Format

Send to

Choose Destination
See comment in PubMed Commons below
Acc Chem Res. 2006 Sep;39(9):628-34.

The aggregation and fibrillation of alpha-synuclein.

Author information

1
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA. enzyme@cats.ucsc.edu

Abstract

alpha-Synuclein is a small (14 kDa), abundant, intrinsically disordered presynaptic protein, whose aggregation is believed to be a critical step in Parkinson's disease (PD). The kinetics of alpha-synuclein fibrillation are consistent with a nucleation-dependent mechanism, in which the critical early stage of the structural transformation involves a partially folded intermediate. Although the basis for the toxic effects of aggregated alpha-synuclein are unknown, it has been proposed that transient oligomers are responsible, possibly by forming pores in membranes. In this Account, I discuss our investigations into the molecular basis for alpha-synuclein aggregation/fibrillation, including factors that either accelerate or inhibit fibrillation, effects of molecular crowding, oxidation, point mutations, and lipid membranes, as well as the variety of conformational and oligomeric states that alpha-synuclein can adopt. It is apparent that neuronal cells must have a very fine balance of factors that control the levels and potential aggregation of alpha-synuclein.

PMID:
16981679
DOI:
10.1021/ar050073t
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society
    Loading ...
    Support Center