Mitochondrial diseases of the brain.

Neurodegenerative disorders are debilitating diseases of the brain, characterized by behavioral, motor and cognitive impairments. Ample evidence underpins mitochondrial dysfunction as a central causal factor in the pathogenesis of neurodegenerative disorders including Parkinson's disease, Huntington's disease, Alzheimer's disease, Amyotrophic lateral sclerosis, Friedreich's ataxia and Charcot-Marie-Tooth disease. In this review, we discuss the role of mitochondrial dysfunction such as bioenergetics defects, mitochondrial DNA mutations, gene mutations, altered mitochondrial dynamics (mitochondrial fusion/fission, morphology, size, transport/trafficking, and movement), impaired transcription and the association of mutated proteins with mitochondria in these diseases. We highlight the therapeutic role of mitochondrial bioenergetic agents in toxin and in cellular and genetic animal models of neurodegenerative disorders. We also discuss clinical trials of bioenergetics agents in neurodegenerative disorders. Lastly, we shed light on PGC-1α, TORC-1, AMP kinase, Nrf2-ARE, and Sirtuins as novel therapeutic targets for neurodegenerative disorders.

[1]  S. Dimauro,et al.  Early‐onset familial parkinsonism due to POLG mutations , 2006, Annals of neurology.

[2]  Mark R. Cookson,et al.  The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease , 2010, Nature Reviews Neuroscience.

[3]  R. Swerdlow,et al.  Mitochondrial function in Parkinson's disease cybrids containing an nt2 neuron-like nuclear background. , 2008, Mitochondrion.

[4]  J. Searcy,et al.  Long-term pioglitazone treatment improves learning and attenuates pathological markers in a mouse model of Alzheimer's disease. , 2012, Journal of Alzheimer's disease : JAD.

[5]  Parvesh Bubber,et al.  Mitochondrial abnormalities in Alzheimer brain: Mechanistic implications , 2005, Annals of neurology.

[6]  R. Gold,et al.  Mitochondrial haplogroup H correlates with ATP levels and age at onset in Huntington disease , 2010, Journal of Molecular Medicine.

[7]  Olaf Riess,et al.  Cellular and subcellular localization of Huntingtin [corrected] aggregates in the brain of a rat transgenic for Huntington disease. , 2007, The Journal of comparative neurology.

[8]  C. Iadecola,et al.  Amyloid β-Induced Impairments in Hippocampal Synaptic Plasticity Are Rescued by Decreasing Mitochondrial Superoxide , 2011, The Journal of Neuroscience.

[9]  R. Nussbaum,et al.  Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1 , 2004, Science.

[10]  M. Beal,et al.  Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery , 2008, Proceedings of the National Academy of Sciences.

[11]  S. Tabrizi,et al.  Biochemical abnormalities and excitotoxicity in Huntington's disease brain , 1999, Annals of neurology.

[12]  D. Turnbull,et al.  Respiratory chain abnormalities in skeletal muscle from patients with Parkinson's disease , 1991, Journal of the Neurological Sciences.

[13]  C. van Broeckhoven,et al.  Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease , 2008, Human mutation.

[14]  P. Lockhart,et al.  Functional association of the parkin gene promoter with idiopathic Parkinson's disease. , 2002, Human molecular genetics.

[15]  A. Whitworth,et al.  Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1 , 2010, Experimental cell research.

[16]  M. Beal,et al.  Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. , 2009, Antioxidants & redox signaling.

[17]  G. Nappi,et al.  Quantitative study of mitochondrial complex I in platelets of parkinsonian patients , 1998, Movement disorders : official journal of the Movement Disorder Society.

[18]  Xiongwei Zhu,et al.  LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. , 2012, Human molecular genetics.

[19]  Victor S. Van Laar,et al.  The interplay of neuronal mitochondrial dynamics and bioenergetics: Implications for Parkinson's disease , 2013, Neurobiology of Disease.

[20]  M. Beal,et al.  PGC-1alpha, a new therapeutic target in Huntington's disease? , 2006, Cell.

[21]  M. Beal,et al.  Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson's disease , 2004, Experimental Neurology.

[22]  Xiongwei Zhu,et al.  A synergistic dysfunction of mitochondrial fission/fusion dynamics and mitophagy in Alzheimer's disease. , 2010, Journal of Alzheimer's disease : JAD.

[23]  Patrizia Rizzu,et al.  Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism , 2002, Science.

[24]  Ole A. Andreassen,et al.  Neuroprotective Effects of Creatine in a Transgenic Mouse Model of Huntington's Disease , 2000, The Journal of Neuroscience.

[25]  M. Beal,et al.  Mitochondria take center stage in aging and neurodegeneration , 2005, Annals of neurology.

[26]  G. Pasinetti,et al.  Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1α) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis , 2011, Molecular Neurodegeneration.

[27]  M. Beal,et al.  Experimental therapeutics in transgenic mouse models of Huntington's disease , 2004, Nature Reviews Neuroscience.

[28]  M. Beal,et al.  Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease , 2009, Neurochemistry International.

[29]  Xiongwei Zhu,et al.  Parkinson’s disease‐associated DJ‐1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction , 2012, Journal of neurochemistry.

[30]  T. Murphy,et al.  NF-E2-related Factor-2 Mediates Neuroprotection against Mitochondrial Complex I Inhibitors and Increased Concentrations of Intracellular Calcium in Primary Cortical Neurons* , 2003, Journal of Biological Chemistry.

[31]  D. Cleveland,et al.  Selective association of misfolded ALS-linked mutant SOD1 with the cytoplasmic face of mitochondria , 2008, Proceedings of the National Academy of Sciences.

[32]  Trygve E Bakken,et al.  Association between mitochondrial DNA variations and Alzheimer's disease in the ADNI cohort , 2010, Neurobiology of Aging.

[33]  M. F. Beal,et al.  Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2′dG , 2006, Neurology.

[34]  C. Shaw,et al.  Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. , 2007, Human molecular genetics.

[35]  M. Beal,et al.  Hugging tight in Huntington's , 2011, Nature Medicine.

[36]  G. Rosoklija,et al.  Recruitment of the Mitochondrial-Dependent Apoptotic Pathway in Amyotrophic Lateral Sclerosis , 2001, The Journal of Neuroscience.

[37]  T. Yeh,et al.  PINK1 mutants associated with recessive Parkinson’s disease are defective in inhibiting mitochondrial release of cytochrome c , 2007, Neurobiology of Disease.

[38]  S McCarthy,et al.  Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10. , 2004, Toxicology and applied pharmacology.

[39]  M. MacDonald,et al.  Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice. , 2003, Human molecular genetics.

[40]  R. Bordet,et al.  Differential susceptibility to the PPAR-γ agonist pioglitazone in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine rodent models of Parkinson's disease. , 2012, Pharmacological research.

[41]  H. Herzog,et al.  Striatal glucose consumption in chorea-free subjects at risk of Huntington's disease , 1993, Journal of Neurology.

[42]  G. Pasinetti,et al.  Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models , 2013, Neurobiology of Aging.

[43]  Manisha N. Patel,et al.  Mitochondria Are a Major Source of Paraquat-induced Reactive Oxygen Species Production in the Brain* , 2007, Journal of Biological Chemistry.

[44]  S. Rapoport,et al.  Evidence for Physiological Down-regulation of Brain Oxidative Phosphorylation in Alzheimer's Disease , 1996, Experimental Neurology.

[45]  M. MacDonald,et al.  Striatal cells from mutant huntingtin knock-in mice are selectively vulnerable to mitochondrial complex II inhibitor-induced cell death through a non-apoptotic pathway. , 2004, Human molecular genetics.

[46]  D. Butterfield,et al.  The Expression of Several Mitochondrial and Nuclear Genes Encoding the Subunits of Electron Transport Chain Enzyme Complexes, Cytochrome c Oxidase, and NADH Dehydrogenase, in Different Brain Regions in Alzheimer's Disease , 1999, Neurochemical Research.

[47]  M. Beal,et al.  The role of mitochondria in inherited neurodegenerative diseases , 2006, Journal of neurochemistry.

[48]  A. Pestronk,et al.  Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS , 2005, Neurology.

[49]  Robert Hill,et al.  Low platelet mitochondrial complex I and complex II/III activity in early untreated parkinson's disease , 1995, Annals of neurology.

[50]  M. Beal,et al.  Additive neuroprotective effects of creatine and a cyclooxygenase 2 inhibitor against dopamine depletion in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease , 2007, Journal of Molecular Neuroscience.

[51]  Hsueh‐Meei Huang,et al.  Inhibition of the alpha-ketoglutarate dehydrogenase complex alters mitochondrial function and cellular calcium regulation. , 2003, Biochimica et biophysica acta.

[52]  K. Lim,et al.  Jcb: Report , 2022 .

[53]  H. Yoshino,et al.  Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson's disease , 1992, Journal of neural transmission. Parkinson's disease and dementia section.

[54]  D. Borchelt,et al.  Coenzyme Q10 and remacemide hydrochloride ameliorate motor deficits in a Huntington's disease transgenic mouse model , 2001, Neuroscience Letters.

[55]  D. Manners,et al.  Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy , 2000, Annals of neurology.

[56]  M. MacDonald,et al.  Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. , 2004, Human molecular genetics.

[57]  M. Behari,et al.  Ultrastructural Variations in Platelets and Platelet Mitochondria: A Novel Feature in Amyotrophic Lateral Sclerosis , 2011, Ultrastructural pathology.

[58]  E. Masliah,et al.  Mutant Pink1 induces mitochondrial dysfunction in a neuronal cell model of Parkinson’s disease by disturbing calcium flux , 2009, Journal of neurochemistry.

[59]  William M. Mauck,et al.  Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson’s disease , 2004, Neurobiology of Aging.

[60]  R. Swerdlow,et al.  Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture , 2004, Neurobiology of Disease.

[61]  M. Behari,et al.  Mitochondrial Perturbance and Execution of Apoptosis in Platelet Mitochondria of Patients With Amyotrophic Lateral Sclerosis , 2011, The International journal of neuroscience.

[62]  J. Bennett,et al.  Relationships among molecular genetic and respiratory properties of Parkinson's disease cybrid cells show similarities to Parkinson's brain tissues. , 2009, Biochimica et biophysica acta.

[63]  P. Aebischer,et al.  Sustained expression of PGC-1α in the rat nigrostriatal system selectively impairs dopaminergic function , 2012, Human molecular genetics.

[64]  D. Bonneau,et al.  Mitochondrial complex I deficiency in GDAP1-related autosomal dominant Charcot-Marie-Tooth disease (CMT2K) , 2009, neurogenetics.

[65]  H. Kawamata,et al.  Different regulation of wild-type and mutant Cu,Zn superoxide dismutase localization in mammalian mitochondria. , 2008, Human molecular genetics.

[66]  John Hardy,et al.  Parkinson's disease , 2009, The Lancet.

[67]  Robert H. Brown,et al.  Amyotrophic Lateral Sclerosis-Associated SOD1 Mutant Proteins Bind and Aggregate with Bcl-2 in Spinal Cord Mitochondria , 2004, Neuron.

[68]  C. Marsden,et al.  Brain, skeletal muscle and platelet homogenate mitochondrial function in Parkinson's disease. , 1992, Brain : a journal of neurology.

[69]  D. Kelly,et al.  PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. , 2006, The Journal of clinical investigation.

[70]  M. Beal,et al.  PGC-1α, a New Therapeutic Target in Huntington's Disease? , 2006, Cell.

[71]  M. Francolini,et al.  Cell culture models to investigate the selective vulnerability of motoneuronal mitochondria to familial ALS‐linked G93ASOD1 , 2006, The European journal of neuroscience.

[72]  M. Beal,et al.  High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain. , 2002, Human molecular genetics.

[73]  G. Sobue,et al.  Mitochondrial Localization of Mutant Superoxide Dismutase 1 Triggers Caspase-dependent Cell Death in a Cellular Model of Familial Amyotrophic Lateral Sclerosis* , 2002, The Journal of Biological Chemistry.

[74]  N. Shibata,et al.  Ultrastructural study of aggregates in the spinal cord of transgenic mice with a G93A mutant SOD1 gene , 2005, Acta Neuropathologica.

[75]  M. Mancuso,et al.  POLG1-Related and other “Mitochondrial Parkinsonisms”: an Overview , 2011, Journal of Molecular Neuroscience.

[76]  S. Petri,et al.  Neural mitochondrial Ca2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn‐superoxide dismutase mutant mice , 2006, Journal of neurochemistry.

[77]  X. Chen,et al.  Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease. , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[78]  B. Spiegelman,et al.  Elevated PGC-1α activity sustains mitochondrial biogenesis and muscle function without extending survival in a mouse model of inherited ALS. , 2012, Cell metabolism.

[79]  Fabienne C. Fiesel,et al.  PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1 , 2010, Nature Cell Biology.

[80]  M. Sporn,et al.  The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. , 2005, Cancer research.

[81]  Shailendra Giri,et al.  5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) attenuates the expression of LPS- and Aβ peptide-induced inflammatory mediators in astroglia , 2005, Journal of Neuroinflammation.

[82]  Tracy L. Niedzielko,et al.  Impaired platelet mitochondrial activity in Alzheimer's disease and mild cognitive impairment. , 2006, Mitochondrion.

[83]  J. Buxbaum,et al.  PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. , 2009, Archives of neurology.

[84]  Xi Chen,et al.  Materials and Methods Som Text Figs. S1 and S2 Table S1 References Abad Directly Links A␤ to Mitochondrial Toxicity in Alzheimer's Disease , 2022 .

[85]  E. Masliah,et al.  α-Synuclein Promotes Mitochondrial Deficit and Oxidative Stress , 2000 .

[86]  L. Barbeito,et al.  Axonal mitochondrial clusters containing mutant SOD1 in transgenic models of ALS. , 2009, Antioxidants & redox signaling.

[87]  Masayuki Yamamoto,et al.  Targeting Nrf2-mediated gene transcription by extremely potent synthetic triterpenoids attenuate dopaminergic neurotoxicity in the MPTP mouse model of Parkinson's disease. , 2013, Antioxidants & redox signaling.

[88]  H. Koh,et al.  Rosiglitazone, a PPAR-γ agonist, protects against striatal dopaminergic neurodegeneration induced by 6-OHDA lesions in the substantia nigra of rats. , 2012, Toxicology letters.

[89]  R. Krüger,et al.  Reduced Basal Autophagy and Impaired Mitochondrial Dynamics Due to Loss of Parkinson's Disease-Associated Protein DJ-1 , 2010, PloS one.

[90]  G. Manfredi,et al.  Mitochondrial function, morphology, and axonal transport in amyotrophic lateral sclerosis. , 2009, Antioxidants & redox signaling.

[91]  Xiongwei Zhu,et al.  Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer's disease patients. , 2008, The American journal of pathology.

[92]  Geng Li,et al.  Coenzyme Q10 Attenuates β-Amyloid Pathology in the Aged Transgenic Mice with Alzheimer Presenilin 1 Mutation , 2008, Journal of Molecular Neuroscience.

[93]  S. Birman,et al.  Chronic Exposure to Rotenone Models Sporadic Parkinson's Disease in Drosophila melanogaster , 2004, The Journal of Neuroscience.

[94]  S. Skatchkov,et al.  Mitochondrial DNA damage is a hallmark of chemically induced and the R6/2 transgenic model of Huntington's disease. , 2009, DNA repair.

[95]  R. Youle,et al.  Neurodegeneration: Trouble in the cell's powerhouse , 2012, Nature.

[96]  C. Januário,et al.  Mitochondrial-dependent apoptosis in Huntington's disease human cybrids , 2010, Experimental Neurology.

[97]  Dwight C. German,et al.  Mitochondria mass is low in mouse substantia nigra dopamine neurons: Implications for Parkinson's disease , 2007, Experimental Neurology.

[98]  A. Navarro,et al.  Pesticides and impairment of mitochondrial function in relation with the parkinsonian syndrome. , 2007, Frontiers in bioscience : a journal and virtual library.

[99]  Olaf Riess,et al.  Cellular and subcellular localization of Huntington aggregates in the brain of a rat transgenic for Huntington disease , 2007 .

[100]  Petteri Piepponen,et al.  Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease , 2011, Cellular and Molecular Life Sciences.

[101]  A. Sarmento-Ribeiro,et al.  Evidence of apoptosis and mitochondrial abnormalities in peripheral blood cells of Huntington's disease patients. , 2008, Biochemical and biophysical research communications.

[102]  Robert W. Taylor,et al.  High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease , 2006, Nature Genetics.

[103]  Robert W. Taylor,et al.  Mitochondrial dysfunction in a cell culture model of familial amyotrophic lateral sclerosis. , 2002, Brain : a journal of neurology.

[104]  P. Puigserver,et al.  Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α , 2006, Cell.

[105]  I. Santana,et al.  Cytochrome c oxidase is decreased in Alzheimer’s disease platelets , 2004, Neurobiology of Aging.

[106]  Joachim Klose,et al.  Mitochondrial Dysfunction and Oxidative Damage in parkin-deficient Mice* , 2004, Journal of Biological Chemistry.

[107]  M. Beal,et al.  Leucine-rich repeat kinase 2: a new player with a familiar theme for Parkinson's disease pathogenesis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[108]  James R. Burke,et al.  Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines , 2002, Nature Neuroscience.

[109]  R. Wu,et al.  Activating mitochondrial regulator PGC-1α expression by astrocytic NGF is a therapeutic strategy for Huntington's disease , 2012, Neuropharmacology.

[110]  G. Dai,et al.  Coenzyme Q10 Reduces β-Amyloid Plaque in an APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease , 2010, Journal of Molecular Neuroscience.

[111]  R. Ferrante,et al.  Combination therapy using minocycline and coenzyme Q10 in R6/2 transgenic Huntington's disease mice. , 2006, Biochimica et biophysica acta.

[112]  R. Benecke,et al.  Electron transfer complexes I and IV of platelets are abnormal in Parkinson's disease but normal in Parkinson-plus syndromes. , 1993, Brain : a journal of neurology.

[113]  Ninds Net-Pd Investigators.  A Pilot Clinical Trial of Creatine and Minocycline in Early Parkinson Disease: 18-Month Results , 2008, Clinical neuropharmacology.

[114]  T. Kaufman,et al.  Quantitative Proteomics of a Presymptomatic A53T α-Synuclein Drosophila Model of Parkinson Disease*S , 2008, Molecular & Cellular Proteomics.

[115]  Robin A. J. Smith,et al.  Targeting an antioxidant to mitochondria decreases cardiac ischemia‐reperfusion injury , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[116]  Robert W Buzzeo,et al.  Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer's transgenic mice. , 2010, Journal of Alzheimer's disease : JAD.

[117]  J. del Río,et al.  Rosiglitazone reverses memory decline and hippocampal glucocorticoid receptor down-regulation in an Alzheimer's disease mouse model. , 2009, Biochemical and biophysical research communications.

[118]  M. Beal,et al.  PINK1 Defect Causes Mitochondrial Dysfunction, Proteasomal Deficit and α-Synuclein Aggregation in Cell Culture Models of Parkinson's Disease , 2009, PloS one.

[119]  A. Storch.  Koenzym Q10 beim Morbus Parkinson , 2007, Der Nervenarzt.

[120]  S. Hosseinkhani,et al.  Complex I and ATP Content Deficiency in Lymphocytes from Friedreich's Ataxia , 2009, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[121]  R. Abagyan,et al.  Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. , 2007, Science.

[122]  M. Beal,et al.  Mitochondrial Approaches for Neuroprotection , 2008, Annals of the New York Academy of Sciences.

[123]  Ernesto Carafoli,et al.  Mitochondrial fission and cristae disruption increase the response of cell models of Huntington's disease to apoptotic stimuli , 2010, EMBO molecular medicine.

[124]  J. Bonnar,et al.  Letter: Prostaglandins and pre-eclampsia. , 1974, Lancet.

[125]  R. Swerdlow,et al.  The Alzheimer's disease mitochondrial cascade hypothesis. , 2010, Journal of Alzheimer's disease : JAD.

[126]  Todd B. Sherer,et al.  Chronic systemic pesticide exposure reproduces features of Parkinson's disease , 2000, Nature Neuroscience.

[127]  S. Pereson,et al.  TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration , 2010, Proceedings of the National Academy of Sciences.

[128]  E. Masliah,et al.  alpha-synuclein promotes mitochondrial deficit and oxidative stress. , 2000, The American journal of pathology.

[129]  T. Ozawa,et al.  Immunohistochemical studies on complexes I, II, III, and IV of mitochondria in parkinson's disease , 1991, Annals of neurology.

[130]  Blake Byers,et al.  LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. , 2011, Cell stem cell.

[131]  Hongmin Wang,et al.  Effects of overexpression of huntingtin proteins on mitochondrial integrity. , 2009, Human molecular genetics.

[132]  Ole A. Andreassen,et al.  Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis , 1999, Nature Medicine.

[133]  J. Andrich,et al.  PGC-1alpha as modifier of onset age in Huntington disease , 2009, Molecular Neurodegeneration.

[134]  Y. Terayama,et al.  Levels of reduced and oxidized coenzymeQ-10 and 8-hydroxy-2′-deoxyguanosine in the cerebrospinal fluid of patients with living Parkinson's disease demonstrate that mitochondrial oxidative damage and/or oxidative DNA damage contributes to the neurodegenerative process , 2010, Neuroscience Letters.

[135]  Ninds Net-Pd Investigators.  A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. , 2006 .

[136]  M. Brini,et al.  Calcium Homeostasis and Mitochondrial Dysfunction in Striatal Neurons of Huntington Disease* , 2008, Journal of Biological Chemistry.

[137]  He Li,et al.  N-Terminal Mutant Huntingtin Associates with Mitochondria and Impairs Mitochondrial Trafficking , 2008, The Journal of Neuroscience.

[138]  A. Pérez-Bouza,et al.  Creatine Supplementation Improves Dopaminergic Cell Survival and Protects against MPP+ Toxicity in an Organotypic Tissue Culture System , 2005, Cell transplantation.

[139]  PINK1 Protects against Oxidative Stress by Phosphorylating Mitochondrial Chaperone TRAP1 , 2007, PLoS biology.

[140]  R. Swerdlow,et al.  Alzheimer's disease cybrids replicate β‐amyloid abnormalities through cell death pathways , 2000 .

[141]  Xiongwei Zhu,et al.  Amyloid-β overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins , 2008, Proceedings of the National Academy of Sciences.

[142]  S. Weis,et al.  Defects of cytochrome c oxidase in the substantia nigra of Parkinson's disease: An immunohistochemical and morphometric study , 1997, Movement disorders : official journal of the Movement Disorder Society.

[143]  P. Reddy,et al.  Assessment of newly synthesized mitochondrial DNA using BrdU labeling in primary neurons from Alzheimer's disease mice: Implications for impaired mitochondrial biogenesis and synaptic damage. , 2011, Biochimica et biophysica acta.

[144]  D. Bonneau,et al.  Mitochondrial dysfunction and pathophysiology of Charcot–Marie–Tooth disease involving GDAP1 mutations , 2011, Experimental Neurology.

[145]  W. Bradley,et al.  Cytochrome c Association with the Inner Mitochondrial Membrane Is Impaired in the CNS of G93A-SOD1 Mice , 2005, The Journal of Neuroscience.

[146]  M. Zeviani,et al.  POLG1 in idiopathic Parkinson disease , 2006, Neurology.

[147]  W. Kunz,et al.  Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis , 1998, Journal of the Neurological Sciences.

[148]  M. Chesselet,et al.  Evidence for behavioral benefits of early dietary supplementation with CoEnzymeQ10 in a slowly progressing mouse model of Huntington's disease , 2012, Molecular and Cellular Neuroscience.

[149]  B R Rosen,et al.  1H NMR spectroscopy studies of Huntington's disease , 1998, Neurology.

[150]  D. Arnold,et al.  Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. , 2012, The New England journal of medicine.

[151]  W. Saxton,et al.  Parkinson's Disease–Associated Kinase PINK1 Regulates Miro Protein Level and Axonal Transport of Mitochondria , 2012, PLoS genetics.

[152]  Anil Kumar,et al.  Effect of resveratrol on 3-nitropropionic acid-induced biochemical and behavioural changes: possible neuroprotective mechanisms , 2006, Behavioural pharmacology.

[153]  R. Swerdlow,et al.  Biochemical Analysis of Cybrids Expressing Mitochondrial DNA from Contursi Kindred Parkinson's Subjects , 2001, Experimental Neurology.

[154]  M. Sikorska,et al.  Paraquat induces oxidative stress, neuronal loss in substantia nigra region and Parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of Coenzyme Q10 , 2009, BMC Neuroscience.

[155]  M. Dalakas,et al.  Cortical motor-sensory hypometabolism in amyotrophic lateral sclerosis: a PET study. , 1988, Journal of computer assisted tomography.

[156]  Ole A. Andreassen,et al.  Therapeutic Effects of Coenzyme Q10 and Remacemide in Transgenic Mouse Models of Huntington's Disease , 2002, The Journal of Neuroscience.

[157]  P. Reddy,et al.  Mitochondria-targeted antioxidants protect against amyloid-beta toxicity in Alzheimer's disease neurons. , 2010, Journal of Alzheimer's disease : JAD.

[158]  M. Seong,et al.  Phase analysis identifies compound heterozygous deletions of the PARK2 gene in patients with early‐onset Parkinson disease , 2012, Clinical genetics.

[159]  J. Gal,et al.  Mitochondrial dysfunction in amyotrophic lateral sclerosis. , 2010, Biochimica et biophysica acta.

[160]  T. Beach,et al.  Dissembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients , 2009, Molecular Neurodegeneration.

[161]  H. Szeto.  Mitochondria-targeted cytoprotective peptides for ischemia-reperfusion injury. , 2008, Antioxidants & redox signaling.

[162]  K. Lyons,et al.  Mitochondrial respiration and respiration‐associated proteins in cell lines created through Parkinson’s subject mitochondrial transfer , 2010, Journal of neurochemistry.

[163]  M. Beal,et al.  Mitochondrial loss, dysfunction and altered dynamics in Huntington's disease. , 2010, Human molecular genetics.

[164]  M. Beal,et al.  Impairment of PGC-1alpha expression, neuropathology and hepatic steatosis in a transgenic mouse model of Huntington's disease following chronic energy deprivation. , 2010, Human molecular genetics.

[165]  Changan Jiang,et al.  Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin , 2006, Nature.

[166]  T. Yeh,et al.  PARK6 PINK1 mutants are defective in maintaining mitochondrial membrane potential and inhibiting ROS formation of substantia nigra dopaminergic neurons. , 2011, Biochimica et biophysica acta.

[167]  V. Fung,et al.  A double‐blind, placebo‐controlled study to assess the mitochondria‐targeted antioxidant MitoQ as a disease‐modifying therapy in Parkinson's disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[168]  David S. Park,et al.  Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics. , 2010, Human molecular genetics.

[169]  Paul Talalay,et al.  Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[170]  H. Szeto,et al.  Cell-permeable Peptide Antioxidants Targeted to Inner Mitochondrial Membrane inhibit Mitochondrial Swelling, Oxidative Cell Death, and Reperfusion Injury* , 2004, Journal of Biological Chemistry.

[171]  P. Tienari,et al.  Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease , 2007, Neurology.

[172]  G. Johnson,et al.  Mitochondrial Respiration and ATP Production Are Significantly Impaired in Striatal Cells Expressing Mutant Huntingtin* , 2005, Journal of Biological Chemistry.

[173]  B. Landwehrmeyer,et al.  Low stability of huntington muscle Mitochondria against Ca2+ in R6/2 mice , 2006, Annals of neurology.

[174]  A. Lang,et al.  Deciphering the role of heterozygous mutations in genes associated with parkinsonism , 2007, The Lancet Neurology.

[175]  D. Santos,et al.  Mitochondrial dynamics and neuronal fate in Parkinson's disease. , 2012, Mitochondrion.

[176]  G. Gibson,et al.  Inactivation and Reactivation of the Mitochondrial α-Ketoglutarate Dehydrogenase Complex* , 2011, The Journal of Biological Chemistry.

[177]  E. Masliah,et al.  Enhanced substantia nigra mitochondrial pathology in human α-synuclein transgenic mice after treatment with MPTP 1 1 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine. , 2004, Experimental Neurology.

[178]  N. Bogdanovic,et al.  PPARγ co-activator-1α (PGC-1α) reduces amyloid-β generation through a PPARγ-dependent mechanism. , 2011, Journal of Alzheimer's disease : JAD.

[179]  C. Crosio,et al.  Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials , 2006, Proceedings of the National Academy of Sciences.

[180]  M. Beal,et al.  Alzheimer's brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[181]  M. Beal,et al.  Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia , 1997, Annals of neurology.

[182]  Jiandie D. Lin,et al.  Defects in Adaptive Energy Metabolism with CNS-Linked Hyperactivity in PGC-1α Null Mice , 2004, Cell.

[183]  D. Brunner,et al.  Comprehensive Behavioral Testing in the R6/2 Mouse Model of Huntington's Disease Shows No Benefit from CoQ10 or Minocycline , 2010, PloS one.

[184]  M. Beal,et al.  Pharmacologic activation of mitochondrial biogenesis exerts widespread beneficial effects in a transgenic mouse model of Huntington's disease. , 2012, Human molecular genetics.

[185]  N. Paricio,et al.  Drosophila DJ-1 mutants are sensitive to oxidative stress and show reduced lifespan and motor deficits. , 2007, Gene.

[186]  M. Beal,et al.  Impaired PGC-1alpha function in muscle in Huntington's disease. , 2009, Human molecular genetics.

[187]  M. Cookson,et al.  LRRK2 Modulates Vulnerability to Mitochondrial Dysfunction in Caenorhabditis elegans , 2009, The Journal of Neuroscience.

[188]  B. Dubois,et al.  Atypical parkinsonism in Guadeloupe: a common risk factor for two closely related phenotypes? , 2007, Brain : a journal of neurology.

[189]  J. Jia,et al.  The association of the regulatory region of the presenilin-2 gene with Alzheimer's disease in the Northern Han Chinese population , 2008, Journal of the Neurological Sciences.

[190]  Michael Courtois,et al.  PGC-1α Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis , 2005, PLoS Biology.

[191]  M. Robin,et al.  Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells , 2003, The Journal of cell biology.

[192]  D. Housman,et al.  The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[193]  O. Poirot,et al.  Expression of mitofusin 2(R94Q) in a transgenic mouse leads to Charcot-Marie-Tooth neuropathy type 2A. , 2010, Brain : a journal of neurology.

[194]  Soumitra S Ghosh,et al.  Use of Cytoplasmic Hybrid Cell Lines for Elucidating the Role of Mitochondrial Dysfunction in Alzheimer's Disease and Parkinson's Disease , 1999, Annals of the New York Academy of Sciences.

[195]  W. Kuhn,et al.  Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with Parkinson's disease , 2003, Neuroscience Letters.

[196]  J. Cooper,et al.  Coenzyme Q10 and vitamin E deficiency in Friedreich’s ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy , 2008, European journal of neurology.

[197]  C. Ross,et al.  A Drosophila model for LRRK2-linked parkinsonism , 2008, Proceedings of the National Academy of Sciences.

[198]  D. Galati,et al.  Accumulation of Amyloid Precursor Protein in the Mitochondrial Import Channels of Human Alzheimer’s Disease Brain Is Associated with Mitochondrial Dysfunction , 2006, The Journal of Neuroscience.

[199]  Joel S Perlmutter,et al.  Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. , 2002, Archives of neurology.

[200]  J. Andersen,et al.  Mitochondrial alpha-synuclein accumulation impairs complex I function in dopaminergic neurons and results in increased mitophagy in vivo , 2010, Neuroscience Letters.

[201]  David S. Park,et al.  DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway , 2010, Proceedings of the National Academy of Sciences.

[202]  Mei Liu,et al.  Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity , 2008, Annals of neurology.

[203]  J. Benito-León,et al.  Respiratory‐chain enzyme activities in isolated mitochondria of lymphocytes from untreated Parkinson's disease patients , 1996, Neurology.

[204]  Ian J. Reynolds,et al.  Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons , 2006, Neurobiology of Disease.

[205]  M. Sporn,et al.  Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes , 2006, Molecular Cancer Therapeutics.

[206]  A. H. V. Schapira,et al.  MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON'S DISEASE , 1989, The Lancet.

[207]  S. Pulst,et al.  Familial multisystem degeneration with parkinsonism associated with the 11778 mitochondrial DNA mutation , 1999, Neurology.

[208]  J. Parks,et al.  High frequency of mitochondrial complex I mutations in Parkinson’s disease and aging , 2004, Neurobiology of Aging.

[209]  M. Beal,et al.  Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders , 2007, Muscle & nerve.

[210]  C. Geula,et al.  Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons , 2006, Nature Genetics.

[211]  C. Schade-Brittinger,et al.  Short‐term effects of coenzyme Q10 in progressive supranuclear palsy: A randomized, placebo‐controlled trial , 2008, Movement disorders : official journal of the Movement Disorder Society.

[212]  N. Avadhani,et al.  Mitochondrial Import and Accumulation of α-Synuclein Impair Complex I in Human Dopaminergic Neuronal Cultures and Parkinson Disease Brain* , 2008, Journal of Biological Chemistry.

[213]  A. Convit,et al.  Reduced hippocampal metabolism in MCI and AD , 2005, Neurology.

[214]  R. Tjian,et al.  In Vitro Analysis of Huntingtin-Mediated Transcriptional Repression Reveals Multiple Transcription Factor Targets , 2005, Cell.

[215]  B. Spiegelman,et al.  Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1α and oxidative phosphorylation , 2008, Proceedings of the National Academy of Sciences.

[216]  P. Reddy,et al.  Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease. , 2011, Human molecular genetics.

[217]  K. Takahashi-Niki,et al.  DJ-1 binds to mitochondrial complex I and maintains its activity. , 2009, Biochemical and biophysical research communications.

[218]  O. Blin,et al.  Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson's disease and multiple system atrophy , 1994, Journal of the Neurological Sciences.

[219]  J. Parks,et al.  Mitochondrial ND5 mutations in idiopathic Parkinson's disease. , 2005, Biochemical and biophysical research communications.

[220]  M. Ankarcrona,et al.  Mitochondrial accumulation of APP and Aβ: significance for Alzheimer disease pathogenesis , 2009, Journal of cellular and molecular medicine.

[221]  Y. Terayama,et al.  Increased mitochondrial oxidative damage in patients with sporadic amyotrophic lateral sclerosis , 2008, Journal of the Neurological Sciences.

[222]  J. Armstrong.  Mitochondria-directed therapeutics. , 2008, Antioxidants & redox signaling.

[223]  M. Chiang,et al.  PPARgamma rescue of the mitochondrial dysfunction in Huntington's disease , 2012, Neurobiology of Disease.

[224]  G. Lenaz,et al.  A Water Soluble CoQ10 Formulation Improves Intracellular Distribution and Promotes Mitochondrial Respiration in Cultured Cells , 2012, PloS one.

[225]  S. Luquet,et al.  Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. , 2006, Cell metabolism.

[226]  O. Andreassen,et al.  Creatine Increases Survival and Delays Motor Symptoms in a Transgenic Animal Model of Huntington's Disease , 2001, Neurobiology of Disease.

[227]  Andre Fischer,et al.  SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis , 2007, The EMBO journal.

[228]  K. Rhodes,et al.  Fumarates Promote Cytoprotection of Central Nervous System Cells against Oxidative Stress via the Nuclear Factor (Erythroid-Derived 2)-Like 2 Pathway , 2012, Journal of Pharmacology and Experimental Therapeutics.

[229]  M. Chesselet,et al.  Bacterial Artificial Chromosome Transgenic Mice Expressing a Truncated Mutant Parkin Exhibit Age-Dependent Hypokinetic Motor Deficits, Dopaminergic Neuron Degeneration, and Accumulation of Proteinase K-Resistant α-Synuclein , 2009, The Journal of Neuroscience.

[230]  Fanny Mochel,et al.  Energy deficit in Huntington disease: why it matters. , 2011, The Journal of clinical investigation.

[231]  Eva Lindqvist,et al.  Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons , 2007, Proceedings of the National Academy of Sciences.

[232]  Timothy H Murphy,et al.  Induction of the Nrf2-driven Antioxidant Response Confers Neuroprotection during Mitochondrial Stress in Vivo* , 2005, Journal of Biological Chemistry.

[233]  M. Gurney,et al.  Metabolic Dysfunction in Familial, but Not Sporadic, Amyotrophic Lateral Sclerosis , 1998, Journal of neurochemistry.

[234]  M. Hayden,et al.  Mitochondrial-Dependent Ca2+ Handling in Huntington's Disease Striatal Cells: Effect of Histone Deacetylase Inhibitors , 2006, The Journal of Neuroscience.

[235]  J. Xie,et al.  Parkinson's Disease Brain Mitochondrial Complex I Has Oxidatively Damaged Subunits and Is Functionally Impaired and Misassembled , 2006, The Journal of Neuroscience.

[236]  M. Beal,et al.  PPAR: a therapeutic target in Parkinson’s disease , 2008, Journal of neurochemistry.

[237]  T. Dawson,et al.  PARIS (ZNF746) Repression of PGC-1α Contributes to Neurodegeneration in Parkinson's Disease , 2011, Cell.

[238]  A. Schapira.  Mitochondrial Dysfunction in Neurodegenerative Diseases , 2008, Neurochemical Research.

[239]  Winnie S. Liang,et al.  Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons , 2008, Proceedings of the National Academy of Sciences.

[240]  M. MacDonald,et al.  HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism. , 2005, Human molecular genetics.

[241]  D. Rubinsztein,et al.  Transcriptional abnormalities in Huntington disease. , 2003, Trends in genetics : TIG.

[242]  O. Andreassen,et al.  Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation , 2001, Journal of neurochemistry.

[243]  E. Valente,et al.  Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. , 2005, Human molecular genetics.

[244]  Sunhong Kim,et al.  Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin , 2006, Nature.

[245]  M. Beal,et al.  Parkinson's disease. , 2007, Human molecular genetics.

[246]  T. Montine,et al.  Mitochondrial DNA Deletions/Rearrangements in Parkinson Disease and Related Neurodegenerative Disorders , 2002, Journal of neuropathology and experimental neurology.

[247]  R. Youle,et al.  Parkin-induced mitophagy in the pathogenesis of Parkinson disease , 2009, Autophagy.

[248]  A. Musarò,et al.  Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. , 2008, Cell metabolism.

[249]  A. Miyawaki,et al.  Identification of Mitochondrial DNA Polymorphisms That Alter Mitochondrial Matrix pH and Intracellular Calcium Dynamics , 2006, PLoS genetics.

[250]  M. Elstner,et al.  Dopaminergic midbrain neurons are the prime target for mitochondrial DNA deletions , 2008, Journal of Neurology.

[251]  A. Schapira,et al.  Mitochondrial matters of the brain: the role in Huntington’s disease , 2010, Journal of bioenergetics and biomembranes.

[252]  Xiaozhong Qiu,et al.  Two point mutations in mitochondrial DNA of cytochrome c oxidase coexist with normal mtDNA in a patient with Alzheimer’s disease , 2001, Brain Research.

[253]  M. Beal,et al.  Neuroprotective effects of creatine , 2011, Amino Acids.

[254]  J. Prehn,et al.  The amyloid precursor protein intracellular domain (AICD) disrupts actin dynamics and mitochondrial bioenergetics , 2010, Journal of neurochemistry.

[255]  Xinnan Wang,et al.  PINK1 and Parkin Target Miro for Phosphorylation and Degradation to Arrest Mitochondrial Motility , 2011, Cell.

[256]  R. Youle,et al.  Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial quality control. , 2011, Antioxidants & redox signaling.

[257]  A Bender,et al.  Creatine supplementation in Parkinson disease: A placebo-controlled randomized pilot trial , 2006, Neurology.

[258]  J. Bennett,et al.  Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells , 2008, Molecular Neurodegeneration.

[259]  S. Lund,et al.  Ca2+-induced permeability transition in human lymphoblastoid cell mitochondria from normal and Huntington’s disease individuals , 2005, Molecular and Cellular Biochemistry.

[260]  C A Ross,et al.  Interference by Huntingtin and Atrophin-1 with CBP-Mediated Transcription Leading to Cellular Toxicity , 2001, Science.

[261]  G. Perry,et al.  Increased Autophagic Degradation of Mitochondria in Alzheimer Disease , 2007, Autophagy.

[262]  M. Sporn,et al.  Triterpenoids CDDO-ethyl amide and CDDO-trifluoroethyl amide improve the behavioral phenotype and brain pathology in a transgenic mouse model of Huntington's disease. , 2010, Free radical biology & medicine.

[263]  R. Hamilton,et al.  Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease , 2009, Proceedings of the National Academy of Sciences.

[264]  Tanner Ek.  PINK1 mutations and differential effects on mitochondrial function , 2010 .

[265]  J. Arenas,et al.  Complex I Defect in muscle from patients with Huntington's disease , 1998, Annals of neurology.

[266]  S. Snyder,et al.  p53 Mediates Cellular Dysfunction and Behavioral Abnormalities in Huntington’s Disease , 2005, Neuron.

[267]  M. Beal,et al.  Mice lacking alpha-synuclein are resistant to mitochondrial toxins , 2006, Neurobiology of Disease.

[268]  A. Kakita,et al.  Patients homozygous and heterozygous for SNCA duplication in a family with parkinsonism and dementia. , 2008, Archives of neurology.

[269]  A. Barrientos,et al.  Cytotoxicity of a mutant huntingtin fragment in yeast involves early alterations in mitochondrial OXPHOS complexes II and III. , 2006, Human molecular genetics.

[270]  Douglass M. Turnbull,et al.  Does the mitochondrial genome play a role in the etiology of Alzheimer’s disease? , 2006, Human Genetics.

[271]  S. Dimauro,et al.  Mitochondrial fusion and function in Charcot–Marie–Tooth type 2A patient fibroblasts with mitofusin 2 mutations , 2008, Experimental Neurology.

[272]  Jiandie D. Lin,et al.  Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators , 2006, Cell.

[273]  Gabriele Siciliano,et al.  Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer’s disease , 2002, Neurobiology of Aging.

[274]  Gary W Miller,et al.  Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson’s disease , 2007, Journal of neurochemistry.

[275]  A. Storch.  [Coenzyme Q10 in Parkinson's disease. Symptomatic or neuroprotective effects?]. , 2007, Der Nervenarzt.

[276]  A. Schapira,et al.  Mitochondrial disease , 2006, The Lancet.

[277]  Ole Gredal,et al.  Toxicity of Familial ALS-Linked SOD1 Mutants from Selective Recruitment to Spinal Mitochondria , 2004, Neuron.

[278]  D. Wells,et al.  Metformin Treatment Has No Beneficial Effect in a Dose-Response Survival Study in the SOD1G93A Mouse Model of ALS and Is Harmful in Female Mice , 2011, PloS one.

[279]  Todd Sherer,et al.  Rotenone Model of Parkinson Disease , 2005, Journal of Biological Chemistry.

[280]  M. Mena,et al.  Susceptibility to rotenone is increased in neurons from parkin null mice and is reduced by minocycline , 2006, Journal of neurochemistry.

[281]  X. Chen,et al.  Mitochondrial Aβ: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease , 2005 .

[282]  R. Youle,et al.  p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both , 2010, Autophagy.

[283]  Yang Zhang,et al.  Effect of β‐amyloid (25–35) on mitochondrial function and expression of mitochondrial permeability transition pore proteins in rat hippocampal neurons , 2011, Journal of cellular biochemistry.

[284]  Lucia Pagani,et al.  Amyloid-Beta Interaction with Mitochondria , 2011, International journal of Alzheimer's disease.

[285]  J. Kong,et al.  Massive Mitochondrial Degeneration in Motor Neurons Triggers the Onset of Amyotrophic Lateral Sclerosis in Mice Expressing a Mutant SOD1 , 1998, The Journal of Neuroscience.

[286]  M. Farrer,et al.  Genomic investigation of α‐synuclein multiplication and parkinsonism , 2008, Annals of neurology.

[287]  A. Kingsbury,et al.  Deficits in a tricarboxylic acid cycle enzyme in brains from patients with Parkinson’s disease , 2003, Neurochemistry International.

[288]  R. Liem,et al.  Mutations in the neurofilament light gene linked to Charcot‐Marie‐Tooth disease cause defects in transport , 2005, Journal of neurochemistry.

[289]  Sebastian Brandner,et al.  Neuroprotective Role of the Reaper-Related Serine Protease HtrA2/Omi Revealed by Targeted Deletion in Mice , 2004, Molecular and Cellular Biology.

[290]  O. Riess,et al.  Localization of sequence variations in PGC-1α influence their modifying effect in Huntington disease , 2011, Molecular Neurodegeneration.

[291]  M. Beal,et al.  Mitochondria targeted therapeutic approaches in Parkinson's and Huntington's diseases , 2013, Molecular and Cellular Neuroscience.

[292]  R. Nussbaum,et al.  Direct Membrane Association Drives Mitochondrial Fission by the Parkinson Disease-associated Protein α-Synuclein*♦ , 2011, The Journal of Biological Chemistry.

[293]  O. Andreassen,et al.  Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. , 2001, Neurobiology of disease.

[294]  Hongyu Zhang,et al.  Combined R-α–lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson’s disease , 2008, Journal of cellular and molecular medicine.

[295]  N. Hattori,et al.  An immunohistochemical study on alpha-ketoglutarate dehydrogenase complex in Parkinson's disease. , 1994, Annals of Neurology.

[296]  M. Beal,et al.  Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis , 2005, Experimental Neurology.

[297]  A. Zippelius,et al.  Impairment of mitochondrial calcium handling in a mtSOD1 cell culture model of motoneuron disease , 2009, BMC Neuroscience.

[298]  N. Wood,et al.  Expanding insights of mitochondrial dysfunction in Parkinson's disease , 2006, Nature Reviews Neuroscience.

[299]  Robert H. Brown,et al.  ALS-linked mutant SOD1 damages mitochondria by promoting conformational changes in Bcl-2 , 2010, Human molecular genetics.

[300]  M. Beal,et al.  Creatine and Cyclocreatine Attenuate MPTP Neurotoxicity , 1998, Experimental Neurology.

[301]  J. Franklin,et al.  The Mitochondria-Targeted Antioxidant MitoQ Prevents Loss of Spatial Memory Retention and Early Neuropathology in a Transgenic Mouse Model of Alzheimer's Disease , 2011, The Journal of Neuroscience.

[302]  I. Santana,et al.  Mitochondria dysfunction of Alzheimer's disease cybrids enhances Aβ toxicity , 2004, Journal of neurochemistry.

[303]  S. Hofmann,et al.  A controlled study of 2 doses of idebenone in the treatment of Alzheimer's disease. , 1997, Neuropsychobiology.

[304]  Pei-Ning Wang,et al.  Heteroplasmy of mitochondrial D310 mononucleotide repeat region in the blood of patients with Alzheimer's disease. , 2009, Journal of Alzheimer's disease : JAD.

[305]  P. Reddy,et al.  Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage. , 2011, Human molecular genetics.

[306]  Y. Smith,et al.  Direct regulation of complex I by mitochondrial MEF2D is disrupted in a mouse model of Parkinson disease and in human patients. , 2011, The Journal of clinical investigation.

[307]  J. Bennett,et al.  Cybrid models of Parkinson's disease show variable mitochondrial biogenesis and genotype-respiration relationships , 2009, Experimental Neurology.

[308]  G. Parati,et al.  Low Anaerobic Threshold and Increased Skeletal Muscle Lactate Production in Subjects with Huntington's Disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[309]  M. Iwata,et al.  Ultrastructural study of synapses in the anterior horn neurons of patients with amyotrophic lateral sclerosis , 1996, Neuroscience Letters.

[310]  Seongman Kang,et al.  Alzheimer's disease-associated amyloid beta interacts with the human serine protease HtrA2/Omi , 2004, Neuroscience Letters.

[311]  M. Beal,et al.  Mutated Human SOD1 Causes Dysfunction of Oxidative Phosphorylation in Mitochondria of Transgenic Mice* , 2002, The Journal of Biological Chemistry.

[312]  Diana Wang,et al.  SIRT1 Suppresses b-Amyloid Production by Activating the a-Secretase Gene ADAM10 , 2010 .

[313]  P. Choudhary,et al.  Early dysregulation of the mitochondrial proteome in a mouse model of Alzheimer's disease. , 2011, Journal of proteomics.

[314]  Todd B. Sherer,et al.  Mechanism of Toxicity in Rotenone Models of Parkinson's Disease , 2003, The Journal of Neuroscience.

[315]  J. Bennett,et al.  The cybrid model of sporadic Parkinson's disease , 2009, Experimental Neurology.

[316]  Margaret A. Johnson,et al.  Mitochondrial enzyme activity in amyotrophic lateral sclerosis: Implications for the role of mitochondria in neuronal cell death , 1999, Annals of neurology.

[317]  O. Andreassen,et al.  Effects of an Inhibitor of Poly(ADP-Ribose) Polymerase, Desmethylselegiline, Trientine, and Lipoic Acid in Transgenic ALS Mice , 2001, Experimental Neurology.

[318]  P. Trimmer,et al.  Differentiated Alzheimer's disease transmitochondrial cybrid cell lines exhibit reduced organelle movement. , 2005, Antioxidants & redox signaling.

[319]  C. Ross,et al.  trans-(−)-ϵ-Viniferin Increases Mitochondrial Sirtuin 3 (SIRT3), Activates AMP-activated Protein Kinase (AMPK), and Protects Cells in Models of Huntington Disease* , 2012, The Journal of Biological Chemistry.

[320]  L. Parnetti,et al.  Idebenone in senile dementia of Alzheimer type: a multicentre study. , 1992, Archives of gerontology and geriatrics.

[321]  Ruben Abagyan,et al.  Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease , 2007, Science.

[322]  R. Burke,et al.  Mutant LRRK2R1441G BAC transgenic mice recapitulate cardinal features of Parkinson's disease , 2009, Nature Neuroscience.

[323]  R. Swerdlow,et al.  Alzheimer's disease cybrids replicate beta-amyloid abnormalities through cell death pathways. , 2000, Annals of neurology.

[324]  A. Pérez-Bouza,et al.  Effects of creatine treatment on the survival of dopaminergic neurons in cultured fetal ventral mesencephalic tissue , 2005, Neuroscience.

[325]  D. Hunter.  Coenzyme Q10 in early Parkinson disease. , 2003, Archives of neurology.

[326]  M. Beal,et al.  Creatine and Its Potential Therapeutic Value for Targeting Cellular Energy Impairment in Neurodegenerative Diseases , 2008, NeuroMolecular Medicine.

[327]  Hui Zhao,et al.  Diammonium Glycyrrhizinate Upregulates PGC-1α and Protects against Aβ1–42-Induced Neurotoxicity , 2012, PloS one.

[328]  T. Videen,et al.  Selective defect of in vivo glycolysis in early Huntington's disease striatum , 2007, Proceedings of the National Academy of Sciences.

[329]  A. Munnich,et al.  Aconitase and mitochondrial iron–sulphur protein deficiency in Friedreich ataxia , 1997, Nature Genetics.

[330]  P. Hemachandra Reddy,et al.  Abnormal mitochondrial dynamics, mitochondrial loss and mutant huntingtin oligomers in Huntington's disease: implications for selective neuronal damage. , 2011, Human molecular genetics.

[331]  R. Swerdlow,et al.  Complex I deficiency in Parkinson's disease frontal cortex , 2008, Brain Research.

[332]  B. Landwehrmeyer,et al.  Impaired Regulation of Brain Mitochondria by Extramitochondrial Ca2+ in Transgenic Huntington Disease Rats* , 2008, Journal of Biological Chemistry.

[333]  J C Mazziotta,et al.  Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease. , 1992, Archives of neurology.

[334]  S. Kuno,et al.  Cytoplasmic transfer of platelet mtDNA from elderly patients with Parkinson's disease to mtDNA-less HeLa cells restores complete mitochondrial respiratory function. , 2001, Biochemical and biophysical research communications.

[335]  M. Sporn,et al.  Neuroprotective Effects of the Triterpenoid, CDDO Methyl Amide, a Potent Inducer of Nrf2-Mediated Transcription , 2009, PloS one.

[336]  M. Beal,et al.  Resveratrol protects against peripheral deficits in a mouse model of Huntington's disease , 2010, Experimental Neurology.

[337]  George Perry,et al.  Impaired Balance of Mitochondrial Fission and Fusion in Alzheimer's Disease , 2009, The Journal of Neuroscience.

[338]  J. Martinou,et al.  Bioenergetic defect associated with mKATP channel opening in a mouse model carrying a mitofusin 2 mutation , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[339]  W. Dauer,et al.  Parkinson's Disease Mechanisms and Models , 2003, Neuron.

[340]  M. Beal,et al.  Combination therapy with Coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s Diseases , 2009, Journal of neurochemistry.

[341]  I. Singh,et al.  Involvement of AMP-activated-protein-kinase (AMPK) in neuronal amyloidogenesis. , 2010, Biochemical and biophysical research communications.

[342]  M. Chesselet,et al.  Adipose tissue dysfunction tracks disease progression in two Huntington's disease mouse models. , 2009, Human molecular genetics.

[343]  R. Krüger,et al.  Mitochondrial translation initiation factor 3 gene polymorphism associated with Parkinson's disease , 2007, Neuroscience Letters.

[344]  L. Petrucelli,et al.  Wild-Type Human TDP-43 Expression Causes TDP-43 Phosphorylation, Mitochondrial Aggregation, Motor Deficits, and Early Mortality in Transgenic Mice , 2010, The Journal of Neuroscience.

[345]  M. Beal,et al.  Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of Parkinsonism , 2008, Journal of neurochemistry.

[346]  L. Tan,et al.  Mitochondrial transcription factor A (TFAM) polymorphisms and risk of late-onset Alzheimer's disease in Han Chinese , 2011, Brain Research.

[347]  M. Varghese,et al.  Mitochondrial NAD+‐linked State 3 respiration and complex‐I activity are compromised in the cerebral cortex of 3‐nitropropionic acid‐induced rat model of Huntington’s disease , 2007, Journal of neurochemistry.

[348]  D. Simon,et al.  Do Somatic Mitochondrial DNA Mutations Contribute to Parkinson's Disease? , 2011, Parkinson's disease.

[349]  M. Beal,et al.  Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer's disease. , 2011, Journal of Alzheimer's disease : JAD.

[350]  R. Swerdlow,et al.  Origin and functional consequences of the complex I defect in Parkinson's disease , 1996, Annals of neurology.

[351]  L. Thompson,et al.  Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for Huntington disease mutation , 2006, Mechanisms of Ageing and Development.

[352]  David S. Park,et al.  Cytoplasmic Pink1 activity protects neurons from dopaminergic neurotoxin MPTP , 2008, Proceedings of the National Academy of Sciences.

[353]  M. Sikorska,et al.  Role of mitochondria in neuronal cell death induced by oxidative stress; neuroprotection by Coenzyme Q10 , 2005, Neurobiology of Disease.

[354]  Robert B. Wilson,et al.  Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue , 1997, Nature Genetics.

[355]  Diana Brahams,et al.  Medicine and the Law , 1983, The Lancet.

[356]  Su Guo,et al.  The PINK1/Parkin pathway regulates mitochondrial dynamics and function in mammalian hippocampal and dopaminergic neurons. , 2011, Human molecular genetics.

[357]  A. Pestronk,et al.  Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III , 2009, Annals of neurology.

[358]  Santosh B Shinde,et al.  Respiratory-chain enzyme activities in isolated mitochondria of lymphocytes from patients with Parkinson's disease: preliminary study. , 2006, Neurology India.

[359]  X. Zhuang,et al.  Paraquat induces dopaminergic dysfunction and proteasome impairment in DJ-1-deficient mice. , 2007, Human molecular genetics.

[360]  M. Beal,et al.  Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis , 2003, Journal of neurochemistry.

[361]  K. Chung,et al.  Alpha‐synuclein impairs normal dynamics of mitochondria in cell and animal models of Parkinson’s disease , 2012, Journal of neurochemistry.

[362]  S. Koh,et al.  Coenzyme Q10 protects against amyloid beta-induced neuronal cell death by inhibiting oxidative stress and activating the P13K pathway. , 2012, Neurotoxicology.

[363]  C. Elger,et al.  Mitochondrial DNA abnormalities in skeletal muscle of patients with sporadic amyotrophic lateral sclerosis. , 2000, Brain : a journal of neurology.

[364]  J. Parks,et al.  Evidence for a defect in NADH , 1990, Neurology.

[365]  H. Pakkenberg,et al.  The clinical syndrome of striatal dopamine deficiency. Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). , 1985, The New England journal of medicine.

[366]  S. Browne,et al.  Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[367]  K. Abe,et al.  Ultrastructural study of mitochondria in the spinal cord of transgenic mice with a G93A mutant SOD1 gene , 2004, Acta Neuropathologica.

[368]  C. Elger,et al.  Visualization of defective mitochondrial function in skeletal muscle fibers of patients with sporadic amyotrophic lateral sclerosis , 1999, Journal of the Neurological Sciences.

[369]  J. Jankovic,et al.  A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease , 2007, Neurology.

[370]  N Howell,et al.  Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[371]  M. Sporn,et al.  Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis. , 2011, Free radical biology & medicine.

[372]  Loren Miraglia,et al.  TORCs: transducers of regulated CREB activity. , 2003, Molecular cell.

[373]  D. Rubinsztein,et al.  Decreased cAMP Response Element-mediated Transcription , 2004, Journal of Biological Chemistry.

[374]  J. Schulz,et al.  Diagnosis and treatment of Friedreich ataxia: a European perspective , 2009, Nature Reviews Neurology.

[375]  T. Siddique,et al.  Hyperactive Intracellular Calcium Signaling Associated with Localized Mitochondrial Defects in Skeletal Muscle of an Animal Model of Amyotrophic Lateral Sclerosis* , 2009, The Journal of Biological Chemistry.

[376]  T. Ozawa,et al.  Point mutations of mitochondrial genome in Parkinson's disease. , 1995, Brain research. Molecular brain research.

[377]  K. Fischbeck,et al.  Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich ataxia. , 2007, Archives of neurology.

[378]  J. Couzin.  Clinical research. Testing a novel strategy against Parkinson's disease. , 2007, Science.

[379]  Xiaomin Song,et al.  Amyloid-β and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice , 2009, Proceedings of the National Academy of Sciences.

[380]  B. Jeon,et al.  α-Synuclein gene duplication is present in sporadic Parkinson disease , 2008, Neurology.

[381]  J. Langston,et al.  Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. , 1983, Science.

[382]  Y. Kagawa,et al.  Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. , 1989, Biochemical and biophysical research communications.

[383]  M. Mancuso,et al.  Mitochondrial DNA rearrangements in young onset parkinsonism: two case reports , 2001, Journal of neurology, neurosurgery, and psychiatry.

[384]  Wayne R Matson,et al.  Dose ranging and efficacy study of high-dose coenzyme Q10 formulations in Huntington's disease mice. , 2006, Biochimica et biophysica acta.

[385]  M. Beal,et al.  Absorption, tolerability, and effects on mitochondrial activity of oral coenzyme Q10 in parkinsonian patients , 1998, Neurology.

[386]  Robert Burke,et al.  Resistance of α-synuclein null mice to the parkinsonian neurotoxin MPTP , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[387]  M. MacDonald,et al.  Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's disease , 2006, Neurobiology of Disease.

[388]  G. McKhann,et al.  Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model , 2010, Proceedings of the National Academy of Sciences.

[389]  Atsushi Tanaka,et al.  PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin , 2010, PLoS biology.

[390]  R. Krüger,et al.  Dissecting the role of the mitochondrial chaperone mortalin in Parkinson's disease: functional impact of disease-related variants on mitochondrial homeostasis. , 2010, Human molecular genetics.

[391]  D. Borchelt,et al.  An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria , 1995, Neuron.

[392]  J. Cooper,et al.  Mitochondrial defect in Huntington's disease caudate nucleus , 1996, Annals of neurology.

[393]  L. Lue,et al.  Inhibition of Amyloid-β (Aβ) Peptide-Binding Alcohol Dehydrogenase-Aβ Interaction Reduces Aβ Accumulation and Improves Mitochondrial Function in a Mouse Model of Alzheimer's Disease , 2011, The Journal of Neuroscience.

[394]  Chunyan Wang,et al.  Leucine‐rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin‐like protein , 2012, Journal of neurochemistry.

[395]  M. Sporn,et al.  Triterpenoid CDDO‐methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer’s disease , 2009, Journal of neurochemistry.

[396]  M. Beal,et al.  Mutant Superoxide Dismutase 1 Forms Aggregates in the Brain Mitochondrial Matrix of Amyotrophic Lateral Sclerosis Mice , 2005, The Journal of Neuroscience.

[397]  Chris J Hass,et al.  Resistance Training With Creatine Monohydrate Improves Upper-Body Strength in Patients With Parkinson Disease: A Randomized Trial , 2007, Neurorehabilitation and neural repair.

[398]  J. Quinn,et al.  Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression. , 2006, Human molecular genetics.

[399]  W. Danysz,et al.  Oral creatine supplementation attenuates L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rats , 2009, Behavioural Brain Research.

[400]  B. Rosen,et al.  Energy metabolism defects in Huntington's disease and effects of coenzyme Q10 , 1997, Annals of neurology.

[401]  Robin A. J. Smith,et al.  Mitochondria‐targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[402]  M. Beal,et al.  Cell‐permeable peptide antioxidants as a novel therapeutic approach in a mouse model of amyotrophic lateral sclerosis , 2006 .

[403]  S. Hersch,et al.  Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice , 2003, Journal of neurochemistry.

[404]  P. van Damme,et al.  G37R SOD1 mutant alters mitochondrial complex I activity, Ca(2+) uptake and ATP production. , 2011, Cell calcium.

[405]  V. Papadopoulos,et al.  Further Evidence on Mitochondrial Targeting of β-Amyloid and Specificity of β-Amyloid-Induced Mitotoxicity in Neurons , 2011, Neurodegenerative Diseases.

[406]  A. Vashisht,et al.  Voltage-dependent Anion Channels (VDACs) Recruit Parkin to Defective Mitochondria to Promote Mitochondrial Autophagy* , 2012, The Journal of Biological Chemistry.

[407]  M. Sikorska,et al.  Water-soluble formulation of Coenzyme Q10 inhibits Bax-induced destabilization of mitochondria in mammalian cells , 2006, Apoptosis.

[408]  M. Farrer,et al.  Genetic variation of the mitochondrial complex I subunit NDUFV2 and Parkinson's disease. , 2010, Parkinsonism & related disorders.

[409]  E. Masliah,et al.  PGC-1α Rescues Huntington’s Disease Proteotoxicity by Preventing Oxidative Stress and Promoting TFEB Function , 2012, Science Translational Medicine.

[410]  P. Reddy,et al.  Amyloid beta impairs mitochondrial anterograde transport and degenerates synapses in Alzheimer's disease neurons. , 2011, Biochimica et biophysica acta.

[411]  D. Hadler,et al.  Sustained efficacy and safety of idebenone in the treatment of Alzheimer's disease: update on a 2-year double-blind multicentre study. , 1998, Journal of neural transmission. Supplementum.

[412]  M. Beal,et al.  Transducer of regulated CREB-binding proteins (TORCs) transcription and function is impaired in Huntington's disease. , 2012, Human molecular genetics.

[413]  A. Whitworth,et al.  Drosophila Parkin requires PINK1 for mitochondrial translocation and ubiquitinates Mitofusin , 2010, Proceedings of the National Academy of Sciences.

[414]  N. Cairns,et al.  TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration , 2009, Proceedings of the National Academy of Sciences.

[415]  Wolfgang Schmid,et al.  Disruption of CREB function in brain leads to neurodegeneration , 2002, Nature Genetics.

[416]  M. Beal,et al.  The Energetics of Huntington's Disease , 2004, Neurochemical Research.

[417]  K. Bushby,et al.  Differential gene expression in a cell culture model of SOD1-related familial motor neurone disease. , 2002, Human molecular genetics.

[418]  M. Trabucchi,et al.  Oxidative metabolism in cultured fibroblasts derived from sporadic Alzheimer's disease (AD) patients , 1997, Neuroscience Letters.

[419]  Kazuyuki Takata,et al.  Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4‐phenylbutyrate, a chemical chaperone , 2007, Journal of neurochemistry.

[420]  S. Dunnett,et al.  Light and electron microscopic characterization of the evolution of cellular pathology in the Hdh(CAG)150 Huntington's disease knock-in mouse , 2012, Brain Research Bulletin.

[421]  O. Andreassen,et al.  Lipoic acid improves survival in transgenic mouse models of Huntington's disease , 2001, Neuroreport.

[422]  M. Mancuso,et al.  Mitochondrial DNA sequence variation and neurodegeneration , 2008, Human Genomics.

[423]  M. Beal,et al.  Somatic mitochondrial DNA mutations in early parkinson and incidental lewy body disease , 2012, Annals of neurology.

[424]  Dimitri Krainc,et al.  Sp1 and TAFII130 Transcriptional Activity Disrupted in Early Huntington's Disease , 2002, Science.

[425]  S. Maruyama,et al.  Ultrastructural study of Bunina bodies in the anterior horn neurons of patients with amyotrophic lateral sclerosis , 1993, Neuroscience Letters.

[426]  Christoph Handschin,et al.  Metabolic control through the PGC-1 family of transcription coactivators. , 2005, Cell metabolism.

[427]  M. Beal,et al.  Marked increase in mitochondrial DNA deletion levels in the cerebral cortex of Huntington's disease patients , 1995, Neurology.

[428]  H. Brown-Borg,et al.  Mitochondrial localization of alpha-synuclein protein in alpha-synuclein overexpressing cells , 2008, Neuroscience Letters.

[429]  Yih-Ru Wu,et al.  Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington's disease patients. , 2007, Biochemical and biophysical research communications.

[430]  R. Swerdlow,et al.  Abnormal Mitochondrial Morphology in Sporadic Parkinson's and Alzheimer's Disease Cybrid Cell Lines , 2000, Experimental Neurology.

[431]  N. Hattori,et al.  An immunohistochemical study on α‐ketoglutarate dehydrogenase complex in Parkinson's disease , 1994 .

[432]  K. Fischbeck,et al.  Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial , 2007, The Lancet Neurology.

[433]  A. Chan,et al.  PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic modifiers of Huntington disease , 2011, Molecular Neurodegeneration.

[434]  P. Reddy,et al.  Mitochondrial structural and functional dynamics in Huntington's disease , 2009, Brain Research Reviews.

[435]  Stanley I. Rapoport,et al.  In vivo PET imaging and postmortem studies suggest potentially reversible and irreversible stages of brain metabolic failure in Alzheimer’s disease , 1999, European Archives of Psychiatry and Clinical Neuroscience.

[436]  Manuel B. Graeber,et al.  PGC-1α, A Potential Therapeutic Target for Early Intervention in Parkinson’s Disease , 2010, Science Translational Medicine.

[437]  E. Seeberg,et al.  Mutant Huntingtin Impairs Axonal Trafficking in Mammalian Neurons In Vivo and In Vitro , 2004, Molecular and Cellular Biology.

[438]  M. Beal,et al.  Bioenergetic approaches for neuroprotection in Parkinson's disease , 2003, Annals of neurology.

[439]  S. Rapoport,et al.  Downregulation of oxidative phosphorylation in Alzheimer disease: loss of cytochrome oxidase subunit mRNA in the hippocampus and entorhinal cortex , 1998, Brain Research.

[440]  J. Melki,et al.  Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits , 2001, Nature Genetics.

[441]  E. Hirsch,et al.  Involvement of mitochondrial complex II defects in neuronal death produced by N-terminus fragment of mutated huntingtin. , 2006, Molecular biology of the cell.

[442]  L. Mucke,et al.  SIRT1 Protects against Microglia-dependent Amyloid-β Toxicity through Inhibiting NF-κB Signaling* , 2005, Journal of Biological Chemistry.

[443]  Jean Féger,et al.  Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe , 2003, Journal of neurochemistry.

[444]  L. Mucke,et al.  SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. , 2005, The Journal of biological chemistry.

[445]  A. Gulino,et al.  Protective effect of pioglitazone, a PPARγ ligand, in a 3 nitropropionic acid model of Huntington's disease , 2011, Brain Research Bulletin.

[446]  J. Nobrega,et al.  Brain Cytochrome Oxidase in Alzheimer's Disease , 1992, Journal of neurochemistry.

[447]  S. Petri,et al.  Decreased mRNA expression of PGC-1α and PGC-1α-regulated factors in the SOD1G93A ALS mouse model and in human sporadic ALS. , 2012, Journal of neuropathology and experimental neurology.

[448]  Mark Ellisman,et al.  MUTANT HUNTINGTIN BINDS THE MITOCHONDRIAL FISSION GTPASE DRP1 AND INCREASES ITS ENZYMATIC ACTIVTY , 2011, Nature Medicine.

[449]  F. Fornai,et al.  Abnormal morphology of peripheral cell tissues from patients with Huntington disease , 2009, Journal of Neural Transmission.

[450]  M. Houshmand,et al.  Huntington’s Disease and Mitochondrial DNA Deletions: Event or Regular Mechanism for Mutant Huntingtin Protein and CAG Repeats Expansion?! , 2007, Cellular and Molecular Neurobiology.

[451]  A. Ludolph,et al.  3-Nitropropionic Acid - Exogenous Animal Neurotoxin and Possible Human Striatal Toxin , 1991, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[452]  E. Tan.  PINK 1 mutations and differential effects on mitochondrial function , 2009 .

[453]  H. Mortiboys,et al.  Mitochondrial impairment in patients with Parkinson disease with the G2019S mutation in LRRK2 , 2010, Neurology.

[454]  M. Parihar,et al.  Mitochondrial association of alpha-synuclein causes oxidative stress , 2008, Cellular and Molecular Life Sciences.

[455]  Jun Wang,et al.  Neuronal SIRT1 Activation as a Novel Mechanism Underlying the Prevention of Alzheimer Disease Amyloid Neuropathology by Calorie Restriction* , 2006, Journal of Biological Chemistry.

[456]  M. Beal,et al.  Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases , 2006, Nature.

[457]  M. Iwata,et al.  Mitochondrial alterations in dorsal root ganglion cells in sporadic amyotrophic lateral sclerosis , 2007, Acta Neuropathologica.

[458]  A. Schapira,et al.  Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. , 2010, Human molecular genetics.

[459]  M. Rapp,et al.  Safety and efficacy of idebenone versus tacrine in patients with Alzheimer's disease: results of a randomized, double-blind, parallel-group multicenter study. , 2002, Pharmacopsychiatry.

[460]  J. Cooper,et al.  Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease , 1998, Annals of neurology.

[461]  J. Götz,et al.  Soluble Beta-Amyloid Leads to Mitochondrial Defects in Amyloid Precursor Protein and Tau Transgenic Mice , 2008, Neurodegenerative Diseases.

[462]  J. Holton,et al.  PINK1 protein in normal human brain and Parkinson's disease. , 2006, Brain : a journal of neurology.

[463]  K. Jellinger,et al.  Unaltered aconitase activity, but decreased complex I activity in substantia nigra pars compacta of patients with Parkinson's disease , 1994, Neuroscience Letters.

[464]  J. Jordán,et al.  The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease. , 2013, Biochimica et biophysica acta.

[465]  M. Carrì,et al.  Mitochondrial dysfunction due to mutant copper/zinc superoxide dismutase associated with amyotrophic lateral sclerosis is reversed by N-acetylcysteine , 2003, Neurobiology of Disease.

[466]  T. Mak,et al.  DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2 , 2006, Proceedings of the National Academy of Sciences.

[467]  C. Filley,et al.  Reduced platelet cytochrome c oxidase activity in Alzheimer's disease , 1994, Neurology.

[468]  Victor Tapias,et al.  A highly reproducible rotenone model of Parkinson's disease , 2009, Neurobiology of Disease.

[469]  N. Bresolin,et al.  Mitochondrial respiratory chain dysfunction in muscle from patients with amyotrophic lateral sclerosis. , 2010, Archives of neurology.

[470]  M. Beal,et al.  Coenzyme Q10 attenuates the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged mice , 1998, Brain Research.

[471]  J. Schulz,et al.  Coenzyme Q10 and nicotinamide and a free radical spin trap protect against MPTP neurotoxicity , 1995, Experimental Neurology.

[472]  G. Johnson,et al.  Mutant Huntingtin Expression Induces Mitochondrial Calcium Handling Defects in Clonal Striatal Cells , 2006, Journal of Biological Chemistry.

[473]  V. Choubey,et al.  Mutant A53T α-Synuclein Induces Neuronal Death by Increasing Mitochondrial Autophagy* , 2011, The Journal of Biological Chemistry.

[474]  B. Hyman,et al.  Age‐Dependent Striatal Excitotoxic Lesions Produced by the Endogenous Mitochondrial Inhibitor Malonate , 1993, Journal of neurochemistry.

[475]  David S. Park,et al.  Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[476]  Josephine C. Dorsman,et al.  Mutant huntingtin represses CBP, but not p300, by binding and protein degradation , 2005, Molecular and Cellular Neuroscience.

[477]  Jie Shen,et al.  Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress , 2008, Proceedings of the National Academy of Sciences.

[478]  A. Kupsch,et al.  Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q(10) in Parkinson disease. , 2007, Archives of neurology.

[479]  J. Schulz,et al.  Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease. , 2005, Human molecular genetics.

[480]  F. Joó,et al.  Ultrastructural evidence for altered calcium in motor nerve terminals in amyotrophc lateral sclerosis , 1996, Annals of neurology.

[481]  David W. Miller,et al.  DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy. , 2011, Human molecular genetics.

[482]  D. Eidelberg,et al.  Metabolic network abnormalities in early Huntington's disease: an [(18)F]FDG PET study. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[483]  Dimitri Krainc,et al.  Transcriptional Repression of PGC-1α by Mutant Huntingtin Leads to Mitochondrial Dysfunction and Neurodegeneration , 2006, Cell.

[484]  F. Castora,et al.  Mutations in mitochondrial‐encoded cytochrome c oxidase subunits I, II, and III genes detected in Alzheimer's disease using single‐strand conformation polymorphism , 2006, Electrophoresis.

[485]  Kathleen M. Schwarz,et al.  Mitochondrial gene therapy augments mitochondrial physiology in a Parkinson's disease cell model. , 2009, Human gene therapy.

[486]  M. Elstner,et al.  Long-term creatine supplementation is safe in aged patients with Parkinson disease. , 2008, Nutrition research.

[487]  H. Szeto,et al.  Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell lines. , 2005, Biochemical pharmacology.

[488]  B. Spiegelman,et al.  Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1α transcription and mitochondrial biogenesis in muscle cells , 2006, Proceedings of the National Academy of Sciences.

[489]  D. Turnbull,et al.  MITOCHONDRIAL FUNCTION IN PARKINSON'S DISEASE , 1989, The Lancet.

[490]  Wenhua Zhang,et al.  Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS , 2003, Annals of neurology.

[491]  L. Thal,et al.  Idebenone treatment fails to slow cognitive decline in Alzheimer’s disease , 2003, Neurology.

[492]  V. Álvarez,et al.  Mutational screening of the mortalin gene (HSPA9) in Parkinson’s disease , 2009, Journal of Neural Transmission.

[493]  L. Guarente,et al.  RETRACTED: SIRT1 Suppresses β-Amyloid Production by Activating the α-Secretase Gene ADAM10 , 2010, Cell.

[494]  M. Beal,et al.  Coenzyme Q10 effects in neurodegenerative disease , 2009, Neuropsychiatric disease and treatment.

[495]  R. Nussbaum,et al.  Parkinson Phenotype in Aged PINK1-Deficient Mice Is Accompanied by Progressive Mitochondrial Dysfunction in Absence of Neurodegeneration , 2009, PloS one.