Document Detail


Α-synuclein neuropathology is controlled by nuclear hormone receptors and enhanced by docosahexaenoic acid in a mouse model for Parkinson's disease.
MedLine Citation:
PMID:  21929559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
α-Synuclein (α-Syn) is a neuronal protein that accumulates progressively in Parkinson's disease (PD) 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 PD-causing A53T mutation in human α-Syn. A diet enriched in DHA, 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 DHA levels. Our results suggest a role for activated RXR/PPARγ 2, obtained by elevated brain PUFA 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; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-31
Journal Detail:
Title:  Brain pathology (Zurich, Switzerland)     Volume:  22     ISSN:  1750-3639     ISO Abbreviation:  Brain Pathol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-13     Completed Date:  2012-08-13     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  9216781     Medline TA:  Brain Pathol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  280-94     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors; Brain Pathology © 2011 International Society of Neuropathology.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / metabolism*,  pathology
Disease Models, Animal
Docosahexaenoic Acids / metabolism*
Mice
Mice, Transgenic
Neurons / metabolism,  pathology
Parkinson Disease / genetics,  metabolism*,  pathology
Receptors, Cytoplasmic and Nuclear / genetics,  metabolism*
alpha-Synuclein / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 NS051318/NS/NINDS NIH HHS; R01 NS051318/NS/NINDS NIH HHS; R01 NS051318-05/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Cytoplasmic and Nuclear; 0/alpha-Synuclein; 25167-62-8/Docosahexaenoic Acids
Comments/Corrections

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