| Α-synuclein neuropathology is controlled by nuclear hormone receptors and enhanced by docosahexaenoic acid in a mouse model for Parkinson's disease. | |
MedLine Citation:
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PMID: 21929559 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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:
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Eugenia Yakunin; Virginie Loeb; Haya Kisos; Yoav Biala; Shlomo Yehuda; Yoel Yaari; Dennis J Selkoe; Ronit Sharon |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-10-31 |
Journal Detail:
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Title: Brain pathology (Zurich, Switzerland) Volume: 22 ISSN: 1750-3639 ISO Abbreviation: Brain Pathol. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-04-13 Completed Date: 2012-08-13 Revised Date: 2013-06-27 |
Medline Journal Info:
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Nlm Unique ID: 9216781 Medline TA: Brain Pathol Country: Switzerland |
Other Details:
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Languages: eng Pagination: 280-94 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors; Brain Pathology © 2011 International Society of Neuropathology. |
Affiliation:
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Department of Biochemistry and Molecular Biology, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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R01 NS051318/NS/NINDS NIH HHS; R01 NS051318/NS/NINDS NIH HHS; R01 NS051318-05/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Cytoplasmic and Nuclear; 0/alpha-Synuclein; 25167-62-8/Docosahexaenoic Acids |
| Comments/Corrections | |
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