Role of post-translational modifications in modulating the structure, function and toxicity of α-synuclein. Implications for Parkinson's disease pathogenesis and therapies

Abid Oueslati, Margot Fournier, Hilal A. Lashuel

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

A better understanding of the molecular and cellular determinants that influence the pathology of Parkinson's disease (PD) is essential for developing effective diagnostic, preventative and therapeutic strategies to treat this devastating disease. A number of post-translational modifications to α-syn are present within the Lewy bodies in the brains of affected patients and transgenic models of PD and related disorders. However, whether disease-associated α-syn post-translational modifications promote or inhibit α-syn aggregation and neurotoxicity in vivo remains unknown. Herein, we summarize and discuss the major disease-associated post-translational modifications (phosphorylation, truncation and ubiquitination) and present our current understanding of the effect of these modifications on α-syn aggregation and toxicity. Elucidating the molecular mechanisms underlying post-translation modifications of α-syn and the consequences of such modifications on the biochemical, structural, aggregation and toxic properties of the protein is essential for unravelling the molecular basis of its function(s) in health and disease. Furthermore, the identification of the natural enzymes involved in regulating the post-translational modifications of α-synuclein will yield novel and more tractable therapeutic targets to treat PD and related synucleinopathies.

Original languageEnglish
Pages (from-to)115-145
Number of pages31
JournalProgress in Brain Research
Volume183
Issue numberC
DOIs
Publication statusPublished - 13 Aug 2010
Externally publishedYes

Fingerprint

Synucleins
Post Translational Protein Processing
Parkinson Disease
Lewy Bodies
Poisons
Ubiquitination
Therapeutics
Phosphorylation
Pathology
Health
Brain
Enzymes
Proteins

Keywords

  • α-synuclein
  • Phosphorylation
  • Post-translationnal modification
  • Truncation
  • Ubiquitination

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Role of post-translational modifications in modulating the structure, function and toxicity of α-synuclein. Implications for Parkinson's disease pathogenesis and therapies. / Oueslati, Abid; Fournier, Margot; Lashuel, Hilal A.

In: Progress in Brain Research, Vol. 183, No. C, 13.08.2010, p. 115-145.

Research output: Contribution to journalArticle

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