alpha-Synuclein Abnormalities in Mouse Models of Peroxisome Biogenesis Disorders
Yakunin, Eugenia Moser, Ann Loeb, Virginie Saada, Ann Faust, Phyllis Crane, Denis I Baes, Myriam Sharon, Ronit # ×
Journal of neuroscience research vol:88 issue:4 pages:866-876
alpha-Synuclein (alpha S) is a presynaptic protein implicated in Parkinson's disease (PD). Growing evidence implicates mitochondrial dysfunction, oxidative stress, and alpha S-lipid interactions in the gradual accumulation of alpha S 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 alpha S-related pathogenesis. We found increased alpha S oligomerization and phosphorylation and its increased deposition in cytoplasmic inclusions in these PBD mouse models. Furthermore, we show that alpha S 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. (C) 2009 Wiley-Liss, Inc.