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Nature 443, 787-795 (19 October 2006) | doi:10.1038/nature05292; Published online 18 October 2006

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Review Article Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases

Michael T. Lin1 & M. Flint Beal1

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Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. Mitochondria are critical regulators of cell death, a key feature of neurodegeneration. Mutations in mitochondrial DNA and oxidative stress both contribute to ageing, which is the greatest risk factor for neurodegenerative diseases. In all major examples of these diseases there is strong evidence that mitochondrial dysfunction occurs early and acts causally in disease pathogenesis. Moreover, an impressive number of disease-specific proteins interact with mitochondria. Thus, therapies targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria, hold great promise.

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