Α-synuclein misfolding and Parkinson's disease.
Substantial evidence links α-synuclein, a small highly conserved presynaptic protein with unknown function, to both familial and sporadic Parkinson's disease (PD). α-Synuclein has been identified as the major component of Lewy bodies and Lewy neurites, the characteristic proteinaceous deposits that are the hallmarks of PD. α-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 α-synuclein and the factors that affect its conformation. This review examines the different aggregation states of α-synuclein, the molecular mechanism of its aggregation, and the influence of environmental and genetic factors on this process.
Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Leonid
L
Breydo
Jessica W
JW
Wu
Vladimir N
VN
Uversky
D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D051844:alpha-Synuclein / Q000378:metabolism*
D051844:alpha-Synuclein