α‐Synuclein metabolism and aggregation is linked to ubiquitin‐independent degradation by the proteasome
- 9 November 2001
- journal article
- Published by Wiley in FEBS Letters
- Vol. 509 (1), 22-26
- https://doi.org/10.1016/s0014-5793(01)03115-5
Abstract
Alpha-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 alpha-synuclein is sufficient to induce inclusion formation in SH-SY5Y cells. In this cellular model, proteasome inhibition leads to an increase of alpha-synuclein accumulation in vivo without ubiquitylation. In accordance, we find that in vitro, unmodified alpha-synuclein can be directly degraded by the 20S proteasome. These findings suggest an ubiquitin-independent mechanism of proteasomal degradation for alpha-synuclein and other natively unfolded proteins.This publication has 32 references indexed in Scilit:
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