Oxidative stress and mitochondrial dysfunction in neurodegeneration.
Rapid advances are being made in our understanding of the pathogenesis of neurodegenerative diseases, particularly those in which specific DNA mutations have been identified. beta-amyloid has been shown to induce free radical formation both directly and via an effect on endothelial function. There is presuasive evidence for cytochrome oxidase dysfunction with oxidative stress and damage in the brains of patients with Alzheimer's disease. The confirmation of the complex II inhibitor 3-nitropropionic acid as a toxin model for Huntington's disease, together with the demonstration of reduced mitochondrial function in Huntington's disease caudate, supports the proposition that mutant huntingtin may exert its effect through an abnormality of energy metabolism.
Schapira
A H
AH
Clinical Neurosciences, Royal Free Hospital School of Medicine, London, UK.
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology; D004249:DNA Damage / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000502:physiology; D005609:Free Radicals; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors
D016564:Amyloid beta-Protein Precursor; D004272:DNA, Mitochondrial; D005609:Free Radicals; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D003576:Electron Transport Complex IV