α-synuclein abnormalities in mouse models of peroxisome biogenesis disorders

Eugenia Yakunin, Ann Moser, Virginie Loeb, Ann Saada, Phyllis Faust, Denis I. Crane, Myriam Baes, Ronit Sharon

Research output: Contribution to journalArticlepeer-review

Abstract

α-Synuclein (αS) is a presynaptic protein implicated in Parkinson's disease (PD). Growing evidence implicates mitochondrial dysfunction, oxidative stress, and αS-lipid interactions in the gradual accumulation of αS in pathogenic forms and its deposition in Lewy bodies, the pathological hallmark of PD and related synucleinopathies. The peroxisomal biogenesis disorders (PBD), with Zellweger syndrome serving as the prototype of this group, are characterized by malformed and functionally impaired peroxisomes. Here we utilized the PBD mouse models Pex2-/-, Pex5-/-, and Pex13-/- to study the potential effects of peroxisomal dysfunction on αS-related pathogenesis. We found increased αS oligomerization and phosphorylation and its increased deposition in cytoplasmic inclusions in these PBD mouse models. Furthermore, we show that αS abnormalities correlate with the altered lipid metabolism and, specifically, with accumulation of long chain, n-6 polyunsaturated fatty acids that occurs in the PBD models.

Original languageEnglish (US)
Pages (from-to)866-876
Number of pages11
JournalJournal of neuroscience research
Volume88
Issue number4
DOIs
StatePublished - Mar 2010

Keywords

  • Alpha synuclein
  • Lipids
  • Parkinson's disease
  • Peroxisomes

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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