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Lewy bodies (LB) in the substantia nigra are a cardinal pathological feature of Parkinson's disease, but they occur in a number of neurodegenerative diseases and can be widespread in the nervous system. The characteristics, locations, and composition of LB are reviewed, with particular attention to alpha-synuclein (alpha-SYN), which appears to be the major component of LB. The propensity for alpha-SYN, a presynaptic protein widely expressed in the brain, to aggregate is because of an amyloidogenic central region. The factors that favor the aggregation of alpha-SYN and mechanisms of toxicity are examined, and a mechanism through which aggregates of alpha-SYN could induce mitochondrial dysfunction and/or release of proapoptotic molecules is proposed.
Clifford W. Shults (Tue,) studied this question.