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

FEBS Letters

Layfield, Robert¹  Spillantini, Maria Grazia¹  Tofaris, George K¹ 

[1] Cambridge Centre for Brain Repair and Neurology Department, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK

关键词: α-Synuclein;    20S proteasome;    Lewy body;    LB;    Lewy body;    PD;    Parkinson's disease;    wt;    wild-type;    DLB;    dementia with Lewy bodies;   

DOI  :  10.1016/S0014-5793(01)03115-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown