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    
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.
Eugenia Yakunin; Virginie Loeb; Haya Kisos; Yoav Biala; Shlomo Yehuda; Yoel Yaari; Dennis J Selkoe; Ronit Sharon
Related Documents :
6539279 - Fluoroacetic acid in guar gum.
7741859 - Homocysteine metabolism in pregnancies complicated by neural-tube defects.
1547769 - Phenytoin-folate interactions: differing effects of the sodium salt and the free acid o...
16696179 - Toxicity of a mixture of 2,4-dichlorophenoxyacetic acid and monosoduim methanearsonate ...
3873989 - Folate analogues as substrates of mammalian folylpolyglutamate synthetase.
14703969 - Combination strategies to enhance transdermal permeation of zidovudine (azt).
18328679 - Critical micellar concentrations of keto derivatives of selected bile acids: thermodyna...
22326489 - Novel s-acyl glutathione derivatives prevent amyloid oxidative stress and cholinergic d...
24158489 - Synergy of ferrous ion on 5-aminolevulinic acid mediated growth inhibition of plasmodiu...
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.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Brain / metabolism*,  pathology
Disease Models, Animal
Docosahexaenoic Acids / metabolism*
Mice, Transgenic
Neurons / metabolism,  pathology
Parkinson Disease / genetics,  metabolism*,  pathology
Receptors, Cytoplasmic and Nuclear / genetics,  metabolism*
alpha-Synuclein / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Receptors, Cytoplasmic and Nuclear; 0/alpha-Synuclein; 25167-62-8/Docosahexaenoic Acids

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Radiologic Features of Granulomatous Mastitis.
Next Document:  Genetic re-identification and antifungal susceptibility testing of Aspergillus section Nigri strains...