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α‐Synuclein abnormalities in mouse models of peroxisome biogenesis disorders
Author(s) -
Yakunin Eugenia,
Moser Ann,
Loeb Virginie,
Saada Ann,
Faust Phyllis,
Crane Denis I.,
Baes Myriam,
Sharon Ronit
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22246
Subject(s) - peroxisome , zellweger syndrome , biology , biogenesis , pathogenesis , synucleinopathies , alpha synuclein , oxidative stress , microbiology and biotechnology , phosphorylation , parkinson's disease , endocrinology , medicine , biochemistry , disease , receptor , gene , immunology
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. © 2009 Wiley‐Liss, Inc.