α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome

α-Synuclein has been implicated in the pathogenesis of Parkinson's disease based on mutations in familial cases of the disease and its presence in Lewy bodies. Here we show that over-expression of wild-type human α-synuclein is sufficient to induce inclusion formation in SH-SY5Y cells. In this...

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Detalles Bibliográficos
Main Authors: Tofaris, G, Layfield, R, Spillantini, MG
Formato: Journal article
Idioma:English
Publicado: 2001
Descripción
Summary:α-Synuclein has been implicated in the pathogenesis of Parkinson's disease based on mutations in familial cases of the disease and its presence in Lewy bodies. Here we show that over-expression of wild-type human α-synuclein is sufficient to induce inclusion formation in SH-SY5Y cells. In this cellular model, proteasome inhibition leads to an increase of α-synuclein accumulation in vivo without ubiquitylation. In accordance, we find that in vitro, unmodified α-synuclein can be directly degraded by the 20S proteasome. These findings suggest an ubiquitin-independent mechanism of proteasomal degradation for α-synuclein and other natively unfolded proteins. © 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.