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Pesticides directly accelerate the rate of α‐synuclein fibril formation: a possible factor in Parkinson's disease
Author(s) -
Uversky Vladimir N,
Li Jie,
Fink Anthony L
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02597-2
Subject(s) - fibril , rotenone , paraquat , parkinson's disease , chemistry , disease , lewy body , biophysics , alpha synuclein , pesticide , neuroscience , medicine , biology , pathology , biochemistry , mitochondrion , agronomy
Parkinson's disease involves intracellular deposits of α‐synuclein in the form of Lewy bodies and Lewy neurites. The etiology of the disease is unknown, however, several epidemiological studies have implicated environmental factors, especially pesticides. Here we show that several pesticides, including rotenone, dieldrin and paraquat, induce a conformational change in α‐synuclein and significantly accelerate the rate of formation of α‐synuclein fibrils in vitro. We propose that the relatively hydrophobic pesticides preferentially bind to a partially folded intermediate conformation of α‐synuclein, accounting for the observed conformational changes, and leading to association and subsequent fibrillation. These observations suggest one possible underlying molecular basis for Parkinson's disease.