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FASEB J. 2005 Aug;19(10):1377-9. Epub 2005 Jun 9.

Dopamine promotes alpha-synuclein aggregation into SDS-resistant soluble oligomers via a distinct folding pathway.

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  • 1Department of Pathology, The University of Melbourne, Victoria, Australia. r.cappai@unimelb.edu.au

Abstract

Dopamine (DA) and alpha-synuclein (alpha-SN) are two key molecules associated with Parkinson's disease (PD). We have identified a novel action of DA in the initial phase of alpha-SN aggregation and demonstrate that DA induces alpha-SN to form soluble, SDS-resistant oligomers. The DA:alpha-SN oligomeric species are not amyloidogenic as they do not react with thioflavin T and lack the typical amyloid fibril structures as visualized with electron microscopy. Circular dichroism studies indicate that in the presence of lipid membranes DA interacts with alpha-SN, causing an alteration to the structure of the protein. Furthermore, DA inhibited the formation of iron-induced alpha-SN amyloidogenic aggregates, suggesting that DA acts as a dominant modulator of alpha-SN aggregation. These observations support the paradigm emerging for other neurodegenerative diseases that the toxic species is represented by a soluble oligomer and not the insoluble fibril.

PMID:
15946991
[PubMed - indexed for MEDLINE]
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