| Toll-like receptor 4 promotes α-synuclein clearance and survival of nigral dopaminergic neurons. | |
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MedLine Citation:
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PMID: 21801874 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Toll-like receptors (TLRs) mediate innate immunity, and their dysregulation may play a role in α-synucleinopathies, such as Parkinson's disease or multiple system atrophy (MSA). The aim of this study was to define the role of TLR4 in α-synuclein-linked neurodegeneration. Ablation of TLR4 in a transgenic mouse model of MSA with oligodendroglial α-synuclein overexpression augmented motor disability and enhanced loss of nigrostriatal dopaminergic neurons. These changes were associated with increased brain levels of α-synuclein linked to disturbed TLR4-mediated microglial phagocytosis of α-synuclein. Furthermore, tumor necrosis factor-α levels were increased in the midbrain and associated with a proinflammatory astroglial response. Our data suggest that TLR4 ablation impairs the phagocytic response of microglia to α-synuclein and enhances neurodegeneration in a transgenic MSA mouse model. The study supports TLR4 signaling as innate neuroprotective mechanism acting through clearance of α-synuclein. |
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Authors:
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Nadia Stefanova; Lisa Fellner; Markus Reindl; Eliezer Masliah; Werner Poewe; Gregor K Wenning |
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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: 2011-06-14 |
Journal Detail:
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Title: The American journal of pathology Volume: 179 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-01 Completed Date: 2012-04-09 Revised Date: 2012-09-25 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 954-63 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Clinical Neurobiology, Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. nadia.stefanova@i-med.ac.at |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Behavior, Animal Cell Line, Tumor DNA Primers / chemistry Dopaminergic Neurons / metabolism* Enzyme-Linked Immunosorbent Assay Inflammation / metabolism Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Confocal / methods Models, Biological Neurodegenerative Diseases / metabolism Phenotype Substantia Nigra / metabolism* Toll-Like Receptor 4 / metabolism* alpha-Synuclein / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AG022074/AG/NIA NIH HHS; AG18440/AG/NIA NIH HHS; AG5131/AG/NIA NIH HHS; F 4404-B19//Austrian Science Fund FWF; NS044233/NS/NINDS NIH HHS; NS057096/NS/NINDS NIH HHS; P 19989-B05//Austrian Science Fund FWF |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/Toll-Like Receptor 4; 0/alpha-Synuclein |
| Comments/Corrections | |
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