Mitochondrial dysfunction and oxidative stress in Parkinson's disease.
Environmental toxins, genetic predisposition and old age are major risk factors for Parkinson's disease (PD). Although the mechanism(s) underlying selective dopaminergic (DA) neurodegeneration remain unclear, molecular studies in both toxin based models and genetic based models of the disease suggest a major etiologic role for mitochondrial dysfunction in the pathogenesis of PD. Further, recent studies have presented clear evidence for a high burden of mtDNA deletions within the substantia nigra neurons in individuals with PD. Ultimately, an understanding of the molecular events which precipitate DA neurodegeneration in idiopathic PD will enable the development of targeted and effective therapeutic strategies. We review recent advances and current understanding of the genetic factors, molecular mechanisms and animal models of PD.
Onyango
Isaac G
IG
Center for the Study of Neurodegenerative Diseases, University of Virginia School of Medicine, Charlottesville, VA, USA. Onyango@virginia.edu
D000818:Animals; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D004272:DNA, Mitochondrial; D046988:Proteasome Endopeptidase Complex