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α-Synuclein neuropathology is controlled by nuclear hormone receptors and enhanced by docosahexanoic acid in a mouse model for Parkinson's disease.
MedLine Citation:
PMID:  21929559     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
α-synuclein (α-Syn) is a neuronal protein that accumulates progressively in Parkinson's disease and related synucleinopathies. Attempting to identify cellular factors that affect α-Syn neuropathology, we previously reported that polyunsaturated fatty acids (PUFAs) promote α-Syn oligomerization and aggregation in cultured cells. We now report that docosahexaenoic acid (DHA) a 22:6 PUFA affects α-Syn oligomerization by activating retinoic X receptor (RXR) and peroxisome proliferator-activated receptor γ2 (PPARγ2). In addition, we show that dietary changes in brain DHA levels affect α-Syn cytopathology in mice transgenic for the Parkinson's disease-causing A53T mutation in human α-Syn. A diet enriched in docosahexaenoic acid, an activating ligand of RXR, increased the accumulation of soluble and insoluble neuronal α-Syn, neuritic injury and astrocytosis. Conversely, abnormal accumulations of α-Syn and its deleterious effects were significantly attenuated by low dietary docosahexaenoic acid levels. Our results suggest a role for activated RXR/PPARγ 2, obtained by elevated brain polyunsaturated fatty acids levels, in α-Syn neuropathology.
Authors:
Eugenia Yakunin; Virginie Loeb; Haya Kisos; Yoav Biala; Shlomo Yehuda; Yoel Yaari; Dennis J Selkoe; Ronit Sharon
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-20
Journal Detail:
Title:  Brain pathology (Zurich, Switzerland)     Volume:  -     ISSN:  1750-3639     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9216781     Medline TA:  Brain Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 The Authors; Brain Pathology © 2011 International Society of Neuropathology.
Affiliation:
Department of Biochemistry and Molecular Biology and Medical Neurobiology, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. Sha'ari Mishpat College, Hod HaSharon, Israel. Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
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