3, 4-Dihydroxyphenylacetic Acid (DOPAC) impairs α-synuclein interaction with lipids

Wenbo Zhou, Chunmei Long, Anthony L. Fink, Vladimir N. Uversky

Research output: Contribution to journalArticle

Abstract

α-Synuclein (α-Syn) is a small intrinsically disordered presynaptic protein known to form insoluble filamentous inclusions in Parkinson's disease (PD) and other neurodegenerative disorders. Various catecholamines can inhibit the α-Syn fibrillation in vitro. Recently, non-covalent binding of DOPAC (3,4-dihydroxyphenylacetic acid), a normal product of the dopamine metabolism, was shown to inhibit the fibrillation of α-Syn due to the DOPAC-induced stabilization of the normally transient oligomers thus preventing them from subsequent fibril formation (Zhou, et al. J. Mol. Biol. 2009, 388 (3), 597-610). We are showing here that the interaction of DOPAC with α-Syn decreases the binding affinity of α-Syn to lipids, suggesting that DOPAC might lead to the gain-of-toxicity of α-Syn aggregates and loss-of-function of α-Syn, both of which could be related to progression of PD.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalOpen Proteomics Journal
Volume3
DOIs
StatePublished - Feb 4 2010

Keywords

  • α-synuclein
  • Aggregation
  • Intrinsically disordered protein
  • Oligomerization
  • Parkinson's disease

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