Journal
NEUROTOXICOLOGY
Volume 23, Issue 4-5, Pages 527-536Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0161-813X(02)00067-0
Keywords
alpha-synuclein; aggregation; fibrils; pesticides; metals
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Funding
- NINDS NIH HHS [R01 NS39985] Funding Source: Medline
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Aggregation of alpha-synuclein has been implicated in the formation of proteinaceous inclusions in the brain (Lewy bodies, Lewy neurites) that are characteristic of neurodegenerative diseases, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLBs). The etiology of PD is unknown, but recent work has shown that except in rare cases, there appears to be no direct genetic basis. However, several studies have implicated environmental factors, especially pesticides and metals. Here we show that certain pesticides and metals induce a conformational change in a-synuclein and directly accelerate the rate of formation of alpha-synuclein fibrils in vitro. In addition, the simultaneous presence of metal and pesticide led to synergistic effects on the rate of fibrillation. We propose a model in which environmental factors in conjunction with genetic susceptibility may form the underlying molecular basis for idiopathic PD. (C) 2002 Elsevier Science Inc. All rights reserved.
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