Age related mitochondrial degenerative disorders in humans

Disorders caused by mitochondrial respiratory chain deficiency due to mutations in mitochondrial DNA have varied phenotypes but many involve neurological features often associated with cell loss within specific brain regions. These disorders, along with the increasing evidence of decline in mitochondrial function with ageing, have raised speculation that primary changes in mitochondria could have an important role in age‐related neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). Evidence supporting a role for mitochondria in common neurodegenerative diseases comes from studies with the toxin MPP+ and familial PD, which has been shown to involve proteins such as DJ‐1 and Pink1 (both of which are predicted to have a role in mitochondrial function and oxidative stress). Mutations within the mitochondrial genome have been shown to accumulate with age and in common neurodegenerative diseases. Mitochondrial DNA haplogroups have also been shown to be associated with certain neurodegenerative conditions. This review covers the primary mitochondrial diseases but also discuss the potential role of mitochondria and mitochondrial DNA mutations in mitochondrial and neurodegenerative diseases, in particular in PD and in AD.

[1]  C. Cotman,et al.  Atherosclerotic Lesions and Mitochondria DNA Deletions in Brain Microvessels as a Central Target for the Development of Human AD and AD‐Like Pathology in Aged Transgenic Mice , 2002, Annals of the New York Academy of Sciences.

[2]  T. Ozawa,et al.  Hypothesis. Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases , 1989 .

[3]  D. Turnbull,et al.  Mitochondrial disease in adults: A scale to monitor progression and treatment , 2006, Neurology.

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

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

[6]  Laura C. Greaves,et al.  Mitochondrial DNA mutations in human disease , 2006, IUBMB life.

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

[8]  靖子 波田野.  Novel PINK1 mutations in early-onset parkinsonism , 2005 .

[9]  Vincenzo Bonifati,et al.  Early‐onset Parkinson's disease caused by a compound heterozygous DJ‐1 mutation , 2003, Annals of neurology.

[10]  M. T. Pellecchia,et al.  Mitochondrial DNA haplogroup K is associated with a lower risk of Parkinson's disease in Italians , 2005, European Journal of Human Genetics.

[11]  M. Obrenovich,et al.  Hypoperfusion, Mitochondria Failure, Oxidative Stress, and Alzheimer Disease , 2003, Journal of biomedicine & biotechnology.

[12]  M. Steel,et al.  Improved analyses of human mtDNA sequences support a recent African origin for Homo sapiens. , 1995, Molecular biology and evolution.

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

[14]  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.

[15]  I. McKeith,et al.  Mitochondrial DNA haplogroups and susceptibility to AD and dementia with Lewy bodies , 2000, Neurology.

[16]  A. Lombès,et al.  Organization, dynamics and transmission of mitochondrial DNA: focus on vertebrate nucleoids. , 2006, Biochimica et biophysica acta.

[17]  P. Ince,et al.  Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD , 2001, Neurology.

[18]  A. Abeliovich,et al.  DJ-1 Is a Redox-Dependent Molecular Chaperone That Inhibits α-Synuclein Aggregate Formation , 2004, PLoS biology.

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

[20]  D. Middleton,et al.  mt4216C variant in linkage with the mtDNA TJ cluster may confer a susceptibility to mitochondrial dysfunction resulting in an increased risk of Parkinson's disease in the Irish , 2003, Experimental Gerontology.

[21]  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.

[22]  Mark A. Smith,et al.  Alzheimer Disease and Oxidative Stress , 2002, Journal of biomedicine & biotechnology.

[23]  D. Turnbull,et al.  Neuropathological Aspects of Mitochondrial DNA Disease , 2004, Neurochemical Research.

[24]  D. Turnbull,et al.  Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvement , 2006, Neuropathology and applied neurobiology.

[25]  A. Yashin,et al.  Mitochondrial DNA haplogroups and APOE4 allele are non-independent variables in sporadic Alzheimer's disease , 2001, Human Genetics.

[26]  S. Lewis,et al.  Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD , 2005, Annals of neurology.

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

[28]  George Perry,et al.  Role of mitochondrial dysfunction in Alzheimer's disease , 2002, Journal of neuroscience research.

[29]  Shinsei Minoshima,et al.  Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase , 2000, Nature Genetics.

[30]  A. Padovani,et al.  Neuropathology of mitochondrial diseases , 2007, Bioscience reports.

[31]  G. Perkins,et al.  Insight into mitochondrial structure and function from electron tomography. , 2002, Biochimica et biophysica acta.

[32]  M. Belouchi,et al.  Phylogenetic analysis of the mitochondrial genome indicates significant differences between patients with Alzheimer disease and controls in a French-Canadian founder population. , 1999, American journal of medical genetics.

[33]  A. Bentivoglio,et al.  PINK1 mutations are associated with sporadic early‐onset parkinsonism , 2004, Annals of neurology.

[34]  P. Blumbergs,et al.  In Situ and in Vitro Study of Colocalization and Segregation of α-Synuclein, Ubiquitin, and Lipids in Lewy Bodies , 2000, Experimental Neurology.

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

[36]  L Margulis,et al.  Symbiosis and evolution. , 1971, Scientific American.

[37]  L. Peltonen,et al.  Parkinsonism, premature menopause, and mitochondrial DNA polymerase γ mutations: clinical and molecular genetic study , 2004, The Lancet.

[38]  T. Pozzan,et al.  Mitochondria as all‐round players of the calcium game , 2000, The Journal of physiology.

[39]  H. Soininen,et al.  Mitochondrial DNA polymorphisms as risk factors for Parkinson’s disease and Parkinson’s disease dementia , 2004, Human Genetics.

[40]  Mark A. Wilson,et al.  The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[41]  T. Dawson,et al.  DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase , 2007, Proceedings of the National Academy of Sciences.

[42]  William C. Copeland,et al.  Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase γ , 1996 .

[43]  N. Takahata,et al.  Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[44]  E. Hirsch,et al.  Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. , 2003, Human molecular genetics.

[45]  Bryan L Roth,et al.  Parkin-deficient Mice Exhibit Nigrostriatal Deficits but Not Loss of Dopaminergic Neurons* , 2003, Journal of Biological Chemistry.

[46]  David C Samuels,et al.  What causes mitochondrial DNA deletions in human cells? , 2008, Nature Genetics.

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

[48]  N. Romero,et al.  Apoptosis in mitochondrial myopathies is linked to mitochondrial proliferation. , 2006, Brain : a journal of neurology.

[49]  T. Niki,et al.  DJ‐1 has a role in antioxidative stress to prevent cell death , 2004, EMBO reports.

[50]  J. Haines,et al.  Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. , 2003, American journal of human genetics.

[51]  D. Chan,et al.  Emerging functions of mammalian mitochondrial fusion and fission. , 2005, Human molecular genetics.

[52]  J. Gilbert,et al.  Analysis of European mitochondrial haplogroups with Alzheimer disease risk , 2004, Neuroscience Letters.

[53]  M. Hengartner.  The biochemistry of apoptosis , 2000, Nature.

[54]  D. Turnbull,et al.  Mitochondrial disease--its impact, etiology, and pathology. , 2007, Current topics in developmental biology.

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

[56]  W. Copeland,et al.  Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase gamma. , 1996, Genomics.

[57]  Margaret A. Johnson,et al.  Role of mitochondrial DNA mutations in human aging: Implications for the central nervous system and muscle , 1998, Annals of neurology.

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

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

[60]  D. Harman.  Aging: a theory based on free radical and radiation chemistry. , 1956, Journal of gerontology.

[61]  Denham. Harraan.  AGING: A THEORY BASED ON FREE RADICAL AND RADIATION CHEMISTRY , 1955 .

[62]  D. Turnbull,et al.  Nature of mitochondrial DNA deletions in substantia nigra neurons. , 2008, American journal of human genetics.

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

[64]  J. Nutt,et al.  Familial aggregation of Parkinson disease: a comparative study of early-onset and late-onset disease. , 2002, Archives of neurology.