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α‐Synuclein metabolism and aggregation is linked to ubiquitin‐independent degradation by the proteasome
Author(s) -
Tofaris George K,
Layfield Robert,
Spillantini Maria Grazia
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)03115-5
Subject(s) - proteasome , ubiquitin , microbiology and biotechnology , pathogenesis , in vitro , chemistry , synuclein , in vivo , protein aggregation , protein degradation , inclusion bodies , alpha synuclein , lactacystin , aggresome , parkinson's disease , biology , biochemistry , proteasome inhibitor , disease , genetics , gene , medicine , immunology , recombinant dna
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.