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• W2064080881 abstract "Intraneuronal deposition of alpha-synuclein as fibrils and oxidative stress are both implicated in the pathogenesis of Parkinson's disease. We found that the critical rate-limiting step in nucleation of alpha-synuclein fibrils under physiological conditions is the oxidative formation and accumulation of a dimeric, dityrosine cross-linked prenucleus. Dimer formation is accelerated for the pathogenic A30P and A53T mutant alpha-synucleins, because of their greater propensity to self-interact, which is reflected in the smaller values of the osmotic second virial coefficient compared to that of wild-type synuclein. Our finding that oxidation is an essential step in alpha-synuclein aggregation supports a mechanism of Parkinson's disease pathogenesis in which the separately studied pathogenic factors of oxidative stress and alpha-synuclein aggregation converge at the critical step of alpha-synuclein dimer formation." @default.
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• W2064080881 date "2002-12-20" @default.
• W2064080881 modified "2023-10-14" @default.
• W2064080881 title "Oxidative Dimer Formation Is the Critical Rate-Limiting Step for Parkinson's Disease α-Synuclein Fibrillogenesis" @default.
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• W2064080881 doi "https://doi.org/10.1021/bi026528t" @default.
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