Mitochondrial dysfunction in neurodegenerative disorders and ageing.

In eukaryotic cells, mitochondria are the organelles that produce the majority of adenosine triphosphate (ATP) required for normal neuronal function and survival. ATP is generated by oxidative phosphorylation (OXPHOS) within mitochondria from intermediates, such as NADH and FADH2which are produced by s-oxidation and the Kreb’s cycle.

[1]  T. Ozawa,et al.  Age-dependent increase in deleted mitochondrial DNA in the human heart: possible contributory factor to presbycardia. , 1991, American heart journal.

[2]  G. Kroemer,et al.  Bcl-2 inhibits the mitochondrial release of an apoptogenic protease , 1996, The Journal of experimental medicine.

[3]  J. Haxby,et al.  Neocortical metabolic abnormalities precede nonmemory cognitive defects in early Alzheimer's-type dementia. , 1986, Archives of neurology.

[4]  W. D. Ehmann,et al.  Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease , 1995, Neurology.

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

[6]  S. Leong,et al.  Retrograde transport of horseradish peroxidase by regenerating preganglionic axons in the cat's cervical sympathetic trunk , 1982, Neuroscience Letters.

[7]  C. Marsden,et al.  Alterations in levels of iron, ferritin, and other trace metals in neurodegenerative diseases affecting the basal ganglia , 1992 .

[8]  M. Beal,et al.  Cortical Cytochrome Oxidase Activity Is Reduced in Alzheimer's Disease , 1994, Journal of neurochemistry.

[9]  J. Ávila,et al.  Analysis of microtubule-associated protein tau glycation in paired helical filaments. , 1994, The Journal of biological chemistry.

[10]  J. Cooper,et al.  Quantitation of a mitochondrial DNA deletion in Parkinson's disease , 1992, FEBS letters.

[11]  M W Gray,et al.  The endosymbiont hypothesis revisited. , 1992, International review of cytology.

[12]  P Trouillas,et al.  Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. , 1997, Human molecular genetics.

[13]  M. Beal,et al.  Increased Vulnerability to 3‐Nitropropionic Acid in an Animal Model of Huntington's Disease , 1998, Journal of neurochemistry.

[14]  R. Youle,et al.  Apoptosis and DNA degradation induced by 1-methyl-4-phenylpyridinium in neurons. , 1991, Biochemical and biophysical research communications.

[15]  B. Cohen,et al.  Platelet membrane fluidity in Alzheimer's disease and major depression. , 1987, The American journal of psychiatry.

[16]  E. Land,et al.  Chemically induced Parkinson's disease. II: Intermediates in the oxidation and reduction reactions of the 1-methyl-4-phenyl-2,3-dihydropyridinium ion and its deprotonated form. , 1989, Biochemical and biophysical research communications.

[17]  T. Niwa,et al.  Detection of tetrahydroisoquinoline in parkinsonian brain as an endogenous amine by use of gas chromatography-mass spectrometry. , 1989, Journal of chromatography.

[18]  Y. Agid,et al.  Is the Vulnerability of Neurons in the Substantia Nigra of Patients with Parkinson's Disease Related to Their Neuromelanin Content? , 1992, Journal of neurochemistry.

[19]  W. Martin,et al.  Cortical glucose metabolism in Huntington's disease , 1992, Neurology.

[20]  Y. Mizuno,et al.  Inhibition of mitochondrial respiration by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mouse brain in vivo , 1988, Neuroscience Letters.

[21]  Ò. Miró,et al.  Absence of relationship between the level of electron transport chain activities and aging in human skeletal muscle. , 1996, Biochemical and biophysical research communications.

[22]  N. Arnheim,et al.  Detection of a specific mitochondrial DNA deletion in tissues of older humans. , 1990, Nucleic acids research.

[23]  A. Morley.  The somatic mutation theory of ageing. , 1995, Mutation research.

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

[25]  C. Marsden,et al.  INCREASED NIGRAL IRON CONTENT IN POSTMORTEM PARKINSONIAN BRAIN , 1987, The Lancet.

[26]  C. Ward,et al.  Parkinson's disease in 65 pairs of twins and in a set of quadruplets , 1983, Neurology.

[27]  S. Dimauro,et al.  Recombination via flanking direct repeats is a major cause of large-scale deletions of human mitochondrial DNA. , 1990, Nucleic acids research.

[28]  Patrizia Mecocci,et al.  Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease , 1994, Annals of neurology.

[29]  D. Manners,et al.  Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. Crapo,et al.  Requirement for Superoxide in Excitotoxic Cell Death , 1996, Neuron.

[31]  B. Rosen,et al.  Evidence for irnnairment of energy metabofism in vivo in Huntington's disease using localized 1H NMR spectroscopy , 1993, Neurology.

[32]  C. Eisdorfer,et al.  A comparison of familial and sporadic Alzheimer's disease , 1993, Neurology.

[33]  A. Hausladen,et al.  Superoxide and peroxynitrite inactivate aconitases, but nitric oxide does not. , 1994, The Journal of biological chemistry.

[34]  J. Taanman,et al.  The mitochondrial genome: structure, transcription, translation and replication. , 1999, Biochimica et biophysica acta.

[35]  V. Petruzzella,et al.  Reduced transcription of mitochondrial DNA in the senescent rat. Tissue dependence and effect of L-carnitine. , 1990, European journal of biochemistry.

[36]  B. Hyman,et al.  Functional Alterations in Alzheimer's Disease: Selective Loss of Mitochondrial-encoded Cytochrome Oxidase mRNA in the Hippocampal Formation , 1994, Journal of neuropathology and experimental neurology.

[37]  M. Beal,et al.  Oxidative damage in Alzheimer's , 1996, Nature.

[38]  C. Münscher,et al.  Human aging is associated with stochastic somatic mutations of mitochondrial DNA. , 1995, Mutation research.

[39]  D. D. Di Monte,et al.  Mitochondrial poisons cause depletion of reduced glutathione in isolated hepatocytes. , 1992, Archives of biochemistry and biophysics.

[40]  C. Marsden,et al.  Anatomic and Disease Specificity of NADH CoQ1 Reductase (Complex I) Deficiency in Parkinson's Disease , 1990, Journal of neurochemistry.

[41]  R. Schreiber,et al.  Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death , 1990, Nature.

[42]  C. Markham,et al.  Cerebral metabolism and atrophy in huntington's disease determined by 18FDG and computed tomographic scan , 1982, Annals of neurology.

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

[44]  R. Waring,et al.  Xenobiotic metabolism in Parkinson's disease , 1989, Neurology.

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

[46]  W. Gibb,et al.  The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[47]  J. Cooper,et al.  Clinical, biochemical and molecular genetic correlations in Friedreich's ataxia. , 2000, Human molecular genetics.

[48]  J. Johnson,et al.  Mitochondrial role in cell aging , 1980, Experimental Gerontology.

[49]  R. Cussó,et al.  DECLINE IN SKELETAL MUSCLE MITOCHONDRIAL RESPIRATION CHAIN FUNCTION WITH AGEING , 1989, The Lancet.

[50]  B. Crain,et al.  Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients. , 1993, Genomics.

[51]  C. Marsden,et al.  Mitochondrial function in Parkinson's disease , 1992, Annals of neurology.

[52]  B. Hyman,et al.  Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[53]  Y. Agid,et al.  Mitochondrial function and parental sex effect in Huntington's disease , 1990, The Lancet.

[54]  I. Maclennan,et al.  Germinal center cells express bcl‐2 protein after activation by signals which prevent their entry into apoptosis , 1991, European journal of immunology.

[55]  D. Choi,et al.  Ischemia-induced neuronal apoptosis , 1996, Current Opinion in Neurobiology.

[56]  S. Sorbi,et al.  Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain , 1983, Annals of neurology.

[57]  K. Jellinger,et al.  Iron‐Melanin Complex in Substantia Nigra of Parkinsonian Brains: An X‐Ray Microanalysis , 1992, Journal of neurochemistry.

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

[59]  M. Dyer,et al.  Ultrastructural localization of bcl-2 protein. , 1992, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[60]  J. Müller‐Höcker,et al.  Cytochrome-c-oxidase deficient cardiomyocytes in the human heart--an age-related phenomenon. A histochemical ultracytochemical study. , 1989, The American journal of pathology.

[61]  Y. Agid,et al.  Toxic Effects of Iron for Cultured Mesencephalic Dopaminergic Neurons Derived from Rat Embryonic Brains , 1992, Journal of neurochemistry.

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

[63]  A. Harding,et al.  Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies , 1988, Nature.

[64]  Denham Harman,et al.  The Biologic Clock: The Mitochondria? , 1972, Journal of the American Geriatrics Society.

[65]  L. Sayre,et al.  Model study on the bioreduction of paraquat, MPP+, and analogs. Evidence against a "redox cycling" mechanism in MPTP neurotoxicity. , 1987, Biochemical and biophysical research communications.

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

[67]  Masashi Narita,et al.  Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC , 1999, Nature.

[68]  K Herholz,et al.  Clinical deterioration in probable Alzheimer's disease correlates with progressive metabolic impairment of association areas. , 1994, Dementia.

[69]  S. Snyder,et al.  Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[70]  P Riederer,et al.  Selective Increase of Iron in Substantia Nigra Zona Compacta of Parkinsonian Brains , 1991, Journal of neurochemistry.

[71]  H. Horvitz,et al.  The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death. , 1990, Developmental biology.

[72]  John Calvin Reed,et al.  Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA , 1993, Nature.

[73]  R. Ramsay,et al.  Energy-dependent uptake of N-methyl-4-phenylpyridinium, the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, by mitochondria. , 1986, The Journal of biological chemistry.

[74]  S. Ohta,et al.  Postmortem changes in mitochondrial respiratory enzymes in brain and a preliminary observation in Parkinson's disease , 1990, Journal of the Neurological Sciences.

[75]  Michel Koenig,et al.  Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin , 1997, Nature Genetics.

[76]  M. Beal,et al.  Inhibition of neuronal nitric oxide synthase prevents MPTP–induced parkinsonism in baboons , 1996, Nature Medicine.

[77]  C. Jacq,et al.  Characterization of a histone-like protein extracted from yeast mitochondria. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[78]  C. Marsden,et al.  α‐tocopherol levels in brain are not altered in Parkinson's disease , 1992 .

[79]  R. Oppenheim.  Cell death during development of the nervous system. , 1991, Annual review of neuroscience.

[80]  Douglas C. Miller,et al.  A large kindred with autosomal dominant Parkinson's disease , 1990, Annals of neurology.

[81]  Xiaodong Wang,et al.  Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c , 1996, Cell.

[82]  D. Wallace.  Mitochondrial genetics: a paradigm for aging and degenerative diseases? , 1992, Science.

[83]  M. Beal,et al.  Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age , 1992, Nature Genetics.

[84]  A. Lezza,et al.  Mitochondrial DNA copy number and mitochondrial DNA deletion in adult and senescent rats. , 1992, Mutation research.

[85]  K. Ohno,et al.  Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR analysis. , 1990, Biochemical and biophysical research communications.

[86]  D. Turnbull,et al.  Mitochondrial DNA analysis: polymorphisms and pathogenicity , 1999, Journal of medical genetics.

[87]  J. Kaprio,et al.  Parkinson's disease in a nationwide twin cohort , 1988, Neurology.

[88]  B. Tomlinson,et al.  Histochemical aspects of five limb muscles in old age. An autopsy study. , 1971, Journal of the neurological sciences.

[89]  E. Love,et al.  Parkinson's disease and exposure to agricultural work and pesticide chemicals , 1992, Neurology.

[90]  A. Schapira.  Mitochondrial function in Huntington's disease: Clues for pathogenesis and prospects for treatment , 1997, Annals of neurology.

[91]  W. Nicklas,et al.  Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. , 1985, Life sciences.

[92]  John X. Morris,et al.  Increased risk of dementia in mothers of Alzheimer's disease cases , 1996, Neurology.

[93]  C. Marsden,et al.  Mitochondrial respiratory chain function in multiple system atrophy , 1997, Movement disorders : official journal of the Movement Disorder Society.

[94]  F. Jiménez-Jiménez,et al.  Exposure to well water and pesticides in Parkinson's disease: A case‐control study in the madrid area , 1992, Movement disorders : official journal of the Movement Disorder Society.

[95]  B. Ames,et al.  Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[96]  Hartmut Frenzei,et al.  Age-dependent structural changes in the myocardium of rats. A quantitative light- and electron-microscopic study on the right and left chamber wall , 1984, Mechanisms of Ageing and Development.

[97]  M. V. Van Woert,et al.  Brain peroxidase and catalase in Parkinson disease. , 1975, Archives of neurology.

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

[99]  S. Dimauro,et al.  A direct repeat is a hotspot for large-scale deletion of human mitochondrial DNA. , 1989, Science.

[100]  J. Turrens,et al.  Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. , 1980, The Biochemical journal.

[101]  B Chance,et al.  The cellular production of hydrogen peroxide. , 1972, The Biochemical journal.

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

[103]  D. D. Di Monte,et al.  Inhibition of Monoamine Oxidase Contributes to the Protective Effect of 7‐Nitroindazole Against MPTP Neurotoxicity , 1997, Journal of neurochemistry.

[104]  K. Davies,et al.  The oxidative inactivation of mitochondrial electron transport chain components and ATPase. , 1990, The Journal of biological chemistry.

[105]  S. Dimauro,et al.  Inclusion body myositis and myopathies , 1995, Annals of neurology.

[106]  R. Uitti,et al.  Early onset Parkinson's disease and childhood environment. , 1987, Advances in neurology.

[107]  E. Cadenas,et al.  Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria. , 1977, Archives of biochemistry and biophysics.

[108]  P. Allen,et al.  Generalized mitochondrial dysfunction in Parkinson's disease detected by magnetic resonance spectroscopy of muscle , 1995, Neurology.

[109]  L. Hillered,et al.  Respiratory Activity of Isolated Rat Brain Mitochondria following in vitro Exposure to Oxygen Radicals , 1983, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[110]  J. Müller‐Höcker.  Mitochondria and Ageing , 1992, Brain pathology.

[111]  J. Cooper,et al.  Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: Effect of ageing , 1992, Journal of the Neurological Sciences.

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

[113]  S. Horai,et al.  Is Parkinson's disease a mitochondrial disorder? , 1992, Journal of the Neurological Sciences.

[114]  C. Marsden,et al.  A 31P magnetic resonance spectroscopy study of mitochondrial function in skeletal muscle of patients with Parkinson's disease , 1994, Journal of the Neurological Sciences.

[115]  R. G. Allen,et al.  Oxidative stress as a causal factor in differentiation and aging: a unifying hypothesis , 1990, Experimental Gerontology.

[116]  K. Takeshige,et al.  1-Methyl-4-phenylpyridinium (MPP+) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in bovine heart submitochondrial particles. , 1990, Biochemical and biophysical research communications.

[117]  A. Lees,et al.  Ageing and Parkinson's disease: substantia nigra regional selectivity. , 1991, Brain : a journal of neurology.

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

[119]  J. Morris,et al.  No association found between Alzheimer's disease and a mitochondrial tRNA glutamine gene variant , 1995, Neuroscience Letters.

[120]  J. Casida,et al.  Interaction of 1‐Methyl‐4‐Phenylpyridinium Ion (MPP+) and Its Analogs with the Rotenone/Piericidin Binding Site of NADH Dehydrogenase , 1991, Journal of neurochemistry.

[121]  Paolo Bernardi,et al.  The permeability transition pore as a mitochondrial calcium release channel: A critical appraisal , 1996, Journal of bioenergetics and biomembranes.

[122]  P. Mecocci,et al.  Oxidative damage to mitochondrial DNA shows marked age‐dependent increases in human brain , 1993, Annals of neurology.

[123]  F. Di Virgilio,et al.  Mitochondrial DNA is not fragmented during apoptosis. , 1992, The Journal of biological chemistry.

[124]  R. S. Sohal,et al.  Relationship between superoxide anion radical generation and aging in the housefly, Musca domestica. , 1989, Free radical biology & medicine.

[125]  F. Sanger,et al.  Sequence and organization of the human mitochondrial genome , 1981, Nature.

[126]  R H Hruban,et al.  Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. , 1995, The New England journal of medicine.

[127]  N. Castagnoli,et al.  Oxidation of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidases A and B and suicide inactivation of the enzymes by MPTP. , 1984, Biochemical and biophysical research communications.

[128]  B Chance,et al.  The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. , 1973, The Biochemical journal.

[129]  N Howell,et al.  Clinical mitochondrial genetics , 1999, Journal of medical genetics.

[130]  I. Weinstein,et al.  Mitochondrial DNA is a major cellular target for a dihydrodiol-epoxide derivative of benzo[a]pyrene. , 1980, Science.

[131]  P. R. Gardner,et al.  Aconitase is a sensitive and critical target of oxygen poisoning in cultured mammalian cells and in rat lungs. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[132]  C. Marsden,et al.  A clinical and genetic study of familial Parkinson's disease , 1991, Movement disorders : official journal of the Movement Disorder Society.

[133]  M. Beal,et al.  Marked changes in mitochondrial DNA deletion levels in Alzheimer brains. , 1994, Genomics.

[134]  A. Schapira,et al.  Evidence for mitochondrial dysfunction in Parkinson's disease—a critical appraisal , 2004, Movement disorders : official journal of the Movement Disorder Society.

[135]  G. Barker,et al.  Proton MRS in Huntington's disease , 1994, The Lancet.

[136]  D. Turnbull,et al.  Mammalian mitochondrial genetics: heredity, heteroplasmy and disease. , 1997, Trends in genetics : TIG.

[137]  S. Kish,et al.  Glutathione peroxidase activity in Parkinson's disease brain , 1985, Neuroscience Letters.

[138]  S. Dimauro,et al.  Mitochondria1 involvement in Parkinson's disease , 1993, Neurology.

[139]  D. Shibata,et al.  A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[140]  J. Langston,et al.  Positron emission tomographic evidence for progression of human MPTP‐induced dopaminergic lesions , 1994, Annals of neurology.

[141]  J. Haxby,et al.  Positron emission tomography in Alzheimer's disease , 1986, Neurology.

[142]  T. Ozawa,et al.  Aging-associated deletions of human diaphragmatic mitochondrial DNA. , 1992, American journal of respiratory cell and molecular biology.

[143]  G. Cortopassi,et al.  A mitochondrial DNA clone is associated with increased risk for Alzheimer disease. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[144]  M. MacDonald,et al.  Frataxin gene of Friedreich's ataxia is targeted to mitochondria , 1997, Annals of neurology.

[145]  R. Weindruch,et al.  Age-associated alterations of the mitochondrial genome. , 1997, Free radical biology & medicine.

[146]  K. Jellinger,et al.  Decreased Catalase Activity but Unchanged Superoxide Dismutase Activity in Brains of Patients with Dementia of Alzheimer Type , 1995, Journal of neurochemistry.

[147]  M. Wong-Riley,et al.  Mitochondrial and nuclear gene expression for cytochrome oxidase subunits are disproportionately regulated by functional activity in neurons , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[148]  A. Torroni,et al.  Mitochondrial oxidative phosphorylation defects in parkinson's disease , 1991, Annals of neurology.

[149]  A. Schapira,et al.  Mitochondrial involvement in Parkinson's disease, Huntington's disease, hereditary spastic paraplegia and Friedreich's ataxia. , 1999, Biochimica et biophysica acta.

[150]  Sangkot Marzuki,et al.  MITOCHONDRIAL DNA MUTATIONS AS AN IMPORTANT CONTRIBUTOR TO AGEING AND DEGENERATIVE DISEASES , 1989, The Lancet.

[151]  D. Perl,et al.  Evidence of neuronal oxidative damage in Alzheimer's disease. , 1996, The American journal of pathology.

[152]  T. Chase,et al.  Effect of aging and dopaminomimetic therapy on mitochondrial respiratory function in Parkinson's disease , 1992, Movement disorders : official journal of the Movement Disorder Society.

[153]  G. Zubenko,et al.  Endoplasmic Reticulum Abnormality in Alzheimer's Disease: Selective Alteration in Platelet NADH-Cytochrome C Reductase Activity , 1989, Journal of geriatric psychiatry and neurology.

[154]  H. Pall,et al.  N-methylation of pyridines in Parkinson's disease , 1991, The Lancet.

[155]  B T Hyman,et al.  Functional Alterations in Alzheimer's Disease: Diminution of Cytochrome Oxidase in the Hippocampal Formation , 1993, Journal of neuropathology and experimental neurology.

[156]  E. Bird,et al.  Regional Mitochondrial Respiratory Activity in Huntington's Disease Brain , 1985, Journal of neurochemistry.

[157]  S. W. Davies,et al.  Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[158]  A. Ballabio,et al.  A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3. , 1998, American journal of human genetics.

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

[160]  Robert P. Friedland,et al.  Alzheimer's disease: Anterior-posterior and lateral hemispheric alterations in cortical glucose utilization , 1985, Neuroscience Letters.

[161]  D. D. Di Monte,et al.  Blood lactate in Parkinson's disease , 1991, Annals of neurology.

[162]  K. Suzuki,et al.  Selective inhibition of complex I of the brain electron transport system by tetrahydroisoquinoline. , 1989, Biochemical and biophysical research communications.

[163]  E. Land,et al.  Chemically induced Parkinson's disease: intermediates in the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl-pyridinium ion. , 1987, Biochemical and biophysical research communications.

[164]  R. Steinbrook,et al.  Preferences of homosexual men with AIDS for life-sustaining treatment. , 1986, The New England journal of medicine.

[165]  G. Kroemer,et al.  Mitochondria as regulators of apoptosis: doubt no more. , 1998, Biochimica et biophysica acta.

[166]  M. Hengartner,et al.  Caenorhabditis elegans gene ced-9 protects cells from programmed cell death , 1992, Nature.

[167]  H. Reichmann,et al.  Electron transport chain defects in Alzheimer's disease. , 1994, Neurology.

[168]  B D Ross,et al.  Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington's and Parkinson's diseases , 1998, Neurology.

[169]  J. Poirier,et al.  The specific vulnerability of the substantia nigra to MPTP is related to the presence of transition metals. , 1985, Biochemical and biophysical research communications.

[170]  V. Petruzzella,et al.  Lipid Composition in Synaptic and Nonsynaptic Mitochondria from Rat Brains and Effect of Aging , 1992, Journal of neurochemistry.

[171]  Galper Jb,et al.  The presence of N-formyl-methionyl-tRNA in HeLa cell mitochondria. , 1969 .

[172]  Quantitative allele‐specific PCR: Demonstration of age‐associated accumulation in human tissues of the A→G mutation at nucleotide 3243 in mitochondrial DNA , 1997, Human mutation.

[173]  V. Ingram,et al.  A mitochondrial DNA deletion in normally aging and in Alzheimer brain tissue. , 1993, Neuroreport.

[174]  A. Schapira,et al.  Mitochondrial respiratory chain disorders II: neurodegenerative disorders and nuclear gene defects , 2000, The Lancet.

[175]  Sanford P. Markey,et al.  Chronic parkinsonism secondary to intravenous injection of meperidine analogues , 1979, Psychiatry Research.

[176]  E. Schon,et al.  Evidence that specific mtDNA point mutations may not accumulate in skeletal muscle during normal human aging. , 1996, American journal of human genetics.

[177]  T. Niwa,et al.  Presence of tetrahydroisoquinoline and 2-methyl-tetrahydroquinoline in parkinsonian and normal human brains. , 1987, Biochemical and biophysical research communications.

[178]  G. Paradies,et al.  The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria. , 1992, Biochimica et biophysica acta.

[179]  Y. Wei,et al.  Liver mitochondrial respiratory functions decline with age. , 1989, Biochemical and biophysical research communications.

[180]  D. Turnbull,et al.  Effects of physical activity and age on mitochondrial function. , 1996, QJM : monthly journal of the Association of Physicians.

[181]  D. Butterfield,et al.  Brain Regional Correspondence Between Alzheimer's Disease Histopathology and Biomarkers of Protein Oxidation , 1995, Journal of neurochemistry.

[182]  V. Petruzzella,et al.  Reduced synthesis of mtRNA in isolated mitochondria of senescent rat brain. , 1991, Biochemical and biophysical research communications.

[183]  R. Ferrante,et al.  Neuropathological Classification of Huntington's Disease , 1985, Journal of neuropathology and experimental neurology.

[184]  H. Nohl,et al.  The mitochondrial site of superoxide formation. , 1986, Biochemical and biophysical research communications.

[185]  A. Barbeau,et al.  Pathology of the Heart in Friedreich's Ataxia: Review of the Literature and Report of One Case , 1976, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[186]  K. Jellinger,et al.  Normal Mitochondrial Genome in Brain from Patients with Parkinson's Disease and Complex I Defect , 1990, Journal of neurochemistry.

[187]  B. Summers,et al.  Debrisoquine hydroxylase gene polymorphism and susceptibility to Parkinson's disease , 1992, The Lancet.

[188]  S. W. Davies,et al.  Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic Mice , 1996, Cell.

[189]  N. Tan,et al.  Temperature dependence of estrogen binding: importance of a subzone in the ligand binding domain of a novel piscine estrogen receptor. , 1999, Biochimica et biophysica acta.

[190]  J. Parks,et al.  Cytochrome C Oxidase in Alzheimer's Disease Brain , 1995, Neurology.

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

[192]  A H Schapira,et al.  Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse , 2000, Annals of neurology.

[193]  A. Schapira,et al.  Mitochondrial respiratory chain disorders I: mitochondrial DNA defects , 2000, The Lancet.

[194]  N. Arnheim,et al.  Mosaicism for a specific somatic mitochondrial DNA mutation in adult human brain , 1992, Nature Genetics.

[195]  C. Marsden,et al.  Mitochondrial Complex I Deficiency in Parkinson's Disease , 1990, Lancet.

[196]  S. Dimauro,et al.  Mitochondrial involvement in Alzheimer's disease. , 1999, Biochimica et biophysica acta.

[197]  P. Chagnon,et al.  Distribution of brain cytochrome oxidase activity in various neurodegenerative diseases. , 1995, Neuroreport.

[198]  C. Marsden.  Parkinson's disease in twins. , 1987, Journal of neurology, neurosurgery, and psychiatry.

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

[200]  G. Finocchiaro,et al.  Glucose metabolism alterations in Friedreich's ataxia , 1988, Neurology.

[201]  W. Reik.  Genomic imprinting: a possible mechanism for the parental origin effect in Huntington's chorea. , 1988, Journal of medical genetics.

[202]  P. Patel,et al.  Friedreich's Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion , 1996, Science.

[203]  W. Tatton,et al.  Apoptosis in neurodegenerative diseases: the role of mitochondria. , 1999, Biochimica et biophysica acta.

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

[205]  L. Pikó,et al.  Studies of sequence heterogeneity of mitochondrial DNA from rat and mouse tissues: Evidence for an increased frequency of deletions/additions with aging , 1988, Mechanisms of Ageing and Development.

[206]  C. Marsden,et al.  A Selective Increase in Particulate Superoxide Dismutase Activity in Parkinsonian Substantia Nigra , 1989, Journal of neurochemistry.

[207]  J. Cooper,et al.  Myopathy in vitamin E deficient rats: muscle fibre necrosis associated with disturbances of mitochondrial function. , 1993, Journal of anatomy.

[208]  J. Martinou,et al.  Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene. , 1992, Science.

[209]  S. Papa.  Mitochondrial oxidative phosphorylation changes in the life span. Molecular aspects and physiopathological implications. , 1996, Biochimica et biophysica acta.

[210]  J. Parks,et al.  Abnormalities of the electron transport chain in idiopathic parkinson's disease , 1989, Annals of neurology.

[211]  Epler Jl,et al.  N-formylmethionyl transfer ribonucleic acid in mitochondria from Neurospora. , 1970 .

[212]  C. Marsden,et al.  Decreased Ferritin Levels in Brain in Parkinson's Disease , 1990, Journal of neurochemistry.

[213]  C. Marsden,et al.  Basal Lipid Peroxidation in Substantia Nigra Is Increased in Parkinson's Disease , 1989, Journal of neurochemistry.

[214]  L. Massieu,et al.  Relationship of Dihydropyridine Binding Sites with Calcium‐Dependent Neurotransmitter Release in Synaptosomes , 1988, Journal of neurochemistry.

[215]  David L. Vaux,et al.  Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells , 1988, Nature.

[216]  P. Nagley,et al.  The universality of bioenergetic disease and amelioration with redox therapy. , 1995, Biochimica et biophysica acta.

[217]  M. Beal,et al.  Mitochondria and free radicals in neurodegenerative diseases , 1997 .

[218]  K. Ohno,et al.  Distinct clustering of point mutations in mitochondrial DNA among patients with mitochondrial encephalomyopathies and with Parkinson's disease. , 1991, Biochemical and biophysical research communications.

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

[220]  Manish S. Shah,et al.  A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes , 1993, Cell.

[221]  A. Schapira,et al.  Mitochondrial DNA analysis in Parkinson's disease , 1990, Movement disorders : official journal of the Movement Disorder Society.

[222]  D. Godin,et al.  Parkinson's disease: A disorder due to nigral glutathione deficiency? , 1982, Neuroscience Letters.

[223]  C. Filley,et al.  Cytochrome oxidase deficiency in Alzheimer's disease , 1990, Neurology.

[224]  R. Bucala,et al.  Advanced glycation end products contribute to amyloidosis in Alzheimer disease. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[225]  A. E. Harding,et al.  Parkinson's disease in twins studied with 18F‐dopa and positron emission tomography , 1992, Neurology.

[226]  R. Davis,et al.  Cybrids in Alzheimer's disease: A cellular model of the disease? , 1997, Neurology.

[227]  E. Perry,et al.  Coenzyme a-acetylating enzymes in Alzheimer's disease: Possible cholinergic ‘compartment’ of pyruvate dehydrogenase , 1980, Neuroscience Letters.

[228]  C. Ragan,et al.  Photolabelling of a mitochondrially encoded subunit of NADH dehydrogenase with [3H]dihydrorotenone , 1987, FEBS letters.

[229]  N. Avadhani,et al.  Preferential attack of mitochondrial DNA by aflatoxin B1 during hepatocarcinogenesis. , 1982, Science.

[230]  Y. Agid,et al.  Iron and Aluminum Increase in the Substantia Nigra of Patients with Parkinson's Disease: An X‐Ray Microanalysis , 1991, Journal of neurochemistry.

[231]  Carlos Cepeda,et al.  Enhanced sensitivity to N‐methyl‐D‐aspartate receptor activation in transgenic and knockin mouse models of Huntington's disease , 1999, Journal of neuroscience research.

[232]  S. Srinivasula,et al.  Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade , 1997, Cell.

[233]  P. Nicotera,et al.  Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis , 1997, The Journal of experimental medicine.

[234]  V. Navaratnam,et al.  Ultrastructural changes in atrial myocardium of the ageing rat. , 1981, Journal of anatomy.

[235]  B. Ames,et al.  Endogenous DNA damage as related to cancer and aging. , 1989, Mutation research.

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

[237]  D. A. Clayton,et al.  Replication of animal mitochondrial DNA , 1982, Cell.

[238]  J. Coyle,et al.  Oxidative stress, glutamate, and neurodegenerative disorders. , 1993, Science.

[239]  S. Dimauro,et al.  Transcription and translation of deleted mitochondrial genomes in Kearns-Sayre syndrome: implications for pathogenesis. , 1990, American journal of human genetics.

[240]  Yau-Huei Wei,et al.  Ageing-associated 5 kb deletion in human liver mitochondrial DNA. , 1991, Biochemical and biophysical research communications.

[241]  C. Marsden,et al.  Mitochondrial function, GSH and iron in neurodegeneration and Lewy body diseases , 1998, Journal of the Neurological Sciences.

[242]  T. Dawson,et al.  Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[243]  G. Krishna,et al.  Formation of superoxide and hydroxyl radicals from 1-methyl-4-phenylpyridinium ion (MPP+): reductive activation by NADPH cytochrome P-450 reductase. , 1986, Biochemical and biophysical research communications.

[244]  S. Korsmeyer,et al.  bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes , 1991, Cell.

[245]  T. Chase,et al.  L‐dopa does not affect electron transfer chain enzymes and respiration of rat muscle mitochondria , 1991, Movement disorders : official journal of the Movement Disorder Society.

[246]  J. Idle,et al.  Mutant debrisoquine hydroxylation genes in Parkinson's disease , 1992, The Lancet.

[247]  J. Cooper,et al.  Irreversible Inhibition of Mitochondrial Complex I by 1‐Methyl‐4‐Phenylpyridinium: Evidence for Free Radical Involvement , 1992, Journal of neurochemistry.

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

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

[250]  S. Markey,et al.  1-Methyl-4-phenylpyridine (MPP+) induces oxidative stress in the rodent. , 1986, Life sciences.

[251]  Edward Byrne,et al.  DECLINE IN SKELETAL MUSCLE MITOCHONDRIAL RESPIRATORY CHAIN FUNCTION: POSSIBLE FACTOR IN AGEING , 1989, The Lancet.

[252]  S. Dimauro,et al.  Accumulation of deletions in human mitochondrial DNA during normal aging: analysis by quantitative PCR. , 1992, Biochimica et biophysica acta.

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

[254]  Peter Riederer,et al.  Transition Metals, Ferritin, Glutathione, and Ascorbic Acid in Parkinsonian Brains , 1989, Journal of neurochemistry.

[255]  Y. Nimura,et al.  Deleted mitochondrial DNA in the skeletal muscle of aged individuals. , 1991, Biochemistry international.

[256]  O. Hansson,et al.  Transgenic mice expressing a Huntington's disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[257]  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.