α-Synuclein misfolding and Parkinson's disease

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1822

Review

Breydo, Leonid¹  Wu, Jessica W.²  Uversky, Vladimir N.^1,3 

[1] Univ S Florida, Dept Mol Med, Coll Med, Tampa, FL 33612 USA

[2] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA

[3] Russian Acad Sci, Inst Biol Instrumentat, Pushchino 142290, Moscow Region, Russia

关键词: alpha-Synuclein;    Parkinson's disease;    Neurodegeneration;    Aggregation;    Intrinsically disordered protein;    Metal-exposure;   

DOI  :  10.1016/j.bbadis.2011.10.002

来源: Elsevier

【 摘 要 】

Substantial evidence links alpha-synuclein, a small highly conserved presynaptic protein with unknown function, to both familial and sporadic Parkinson's disease (PD). alpha-Synuclein has been identified as the major component of Lewy bodies and Lewy neurites, the characteristic proteinaceous deposits that are the hallmarks of PD. alpha-Synuclein is a typical intrinsically disordered protein, but can adopt a number of different conformational states depending on conditions and cofactors. These include the helical membrane-bound form, a partially-folded state that is a key intermediate in aggregation and fibrillation, various oligomeric species, and fibrillar and amorphous aggregates. The molecular basis of PD appears to be tightly coupled to the aggregation of alpha-synuclein and the factors that affect its conformation. This review examines the different aggregation states of alpha-synuclein, the molecular mechanism of its aggregation, and the influence of environmental and genetic factors on this process. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

Free