The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis?
Aging is the most important risk factor for common neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Aging in the central nervous system has been associated with elevated mutation load in mitochondrial DNA, defects in mitochondrial respiration and increased oxidative damage. These observations support a 'vicious cycle' theory which states that there is a feedback mechanism connecting these events in aging and age-associated neurodegeneration. Despite being an extremely attractive hypothesis, the bulk of the evidence supporting the mitochondrial vicious cycle model comes from pharmacological experiments in which the modes of mitochondrial enzyme inhibition are far from those observed in real life. Furthermore, recent in vivo evidence does not support this model. In this review, we focus on the relationship among the components of the putative vicious cycle, with particular emphasis on the role of mitochondrial defects on oxidative stress.
Fukui
Hirokazu
H
Neuroscience Program, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Moraes
Carlos T
CT
D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D009410:Nerve Degeneration / Q000503:physiopathology*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I