Increasing evidence has implicated oxidative damage in the pathogenesis of neurodegenerative diseases. The major source of free radicals in the cell is the mitochondria. Peroxynitrite is formed by the reaction of superoxide with nitric oxide, and it produces both oxidative damage and protein nitration. Mutations in CuZn superoxide dismutase associated with familial ALS may result in increased −OH radical generation or in increased reactivity with peroxynitrite to nitrate proteins. There is evidence for increased oxidative damage in Alzheimer's disease and Parkinson's disease in neurons undergoing neurodegenerative changes. A role for oxidative damage in Parkinson's disease toxicity and in Huntington's disease is supported by studies in animal models. Improved antioxidant therapies may prove useful in slowing or halting the progression of neurodegenerative diseases.
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