Oxidative stress and the pathogenesis of Parkinson's disease

摘要: Current concepts of the pathogenesis Parkinson's disease (PD) center on formation reactive oxygen species and onset oxidative stress leading to damage substantia nigra pars compacta. Extensive postmortem studies have provided evidence support involvement in PD; particular, these include alterations brain iron content, impaired mitochondrial function, antioxidant protective systems (most notably superoxide dismutase [SOD] reduced glutathione [GSH]), lipids, proteins, DNA. Iron can induce stress, intranigral injections been shown a model progressive parkinsonism. A loss GSH is associated with incidental Lewy body may represent earliest biochemical marker nigral cell loss. depletion alone not result neurons but increase susceptibility subsequent toxic or free radical exposure. The nature responsible for death PD remains unknown, there hydroxyl (OH.), peroxynitrite, nitric oxide. Indeed, OH. peroxynitrite be critically dependent oxide formation. Central many processes involved are actions monoamine oxidase-B (MAO-B). MAO-B essential activation 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 1-methyl-4-phenylpyridinium ion, component enzymatic conversion dopamine hydrogen peroxide (H2O2), other potential toxins such as isoquinolines beta-carbolines. Thus, inhibition by drugs selegiline protect against some radicals formed from oxidation dopamine. In addition, act through mechanism unrelated neurotrophic factor activity upregulate molecules glutathione, SOD, catalase, BCL-2 protein, which oxidant apoptosis. Consequently, advantageous long-term treatment PD.