| Synphilin-1 attenuates neuronal degeneration in the A53T alpha-synuclein transgenic mouse model. | |
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MedLine Citation:
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PMID: 20185556 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Genetic alterations in alpha-synuclein cause autosomal dominant familial Parkinsonism and may contribute to sporadic Parkinson's disease (PD). Synphilin-1 is an alpha-synuclein-interacting protein, with implications in PD pathogenesis related to protein aggregation. Currently, the in vivo role of synphilin-1 in alpha-synuclein-linked pathogenesis is not fully understood. Using the mouse prion protein promoter, we generated synphilin-1 transgenic mice, which did not display PD-like phenotypes. However, synphilin-1/A53T alpha-synuclein double-transgenic mice survived longer than A53T alpha-synuclein single-transgenic mice. There were attenuated A53T alpha-synuclein-induced motor abnormalities and decreased astroglial reaction and neuronal degeneration in brains in double-transgenic mice. Overexpression of synphilin-1 decreased caspase-3 activation, increased beclin-1 and LC3 II expression and promoted formation of aggresome-like structures, suggesting that synphilin-1 alters multiple cellular pathways to protect against neuronal degeneration. These studies demonstrate that synphilin-1 can diminish the severity of alpha-synucleinopathy and play a neuroprotective role against A53T alpha-synuclein toxicity in vivo. |
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Authors:
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Wanli W Smith; Zhaohui Liu; Yideng Liang; Naoki Masuda; Debbie A Swing; Nancy A Jenkins; Neal G Copeland; Juan C Troncoso; Mikhail Pletnikov; Ted M Dawson; Lee J Martin; Timothy H Moran; Michael K Lee; David R Borchelt; Christopher A Ross |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-02-25 |
Journal Detail:
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Title: Human molecular genetics Volume: 19 ISSN: 1460-2083 ISO Abbreviation: Hum. Mol. Genet. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-07 Completed Date: 2010-09-22 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 9208958 Medline TA: Hum Mol Genet Country: England |
Other Details:
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Languages: eng Pagination: 2087-98 Citation Subset: IM |
Affiliation:
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Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Apoptosis Regulatory Proteins / metabolism Brain / metabolism, pathology* Carrier Proteins / genetics*, metabolism Caspase 3 / metabolism Immunoblotting Immunohistochemistry Lewy Bodies / metabolism Mice Mice, Transgenic Mutation, Missense / genetics Nerve Degeneration / etiology, metabolism* Nerve Tissue Proteins / genetics*, metabolism Parkinson Disease / complications, genetics* alpha-Synuclein / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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NS38377/NS/NINDS NIH HHS; R01NS055252/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/Becn1 protein, mouse; 0/Carrier Proteins; 0/Nerve Tissue Proteins; 0/Sncaip protein, mouse; 0/alpha-Synuclein; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3 |
| Comments/Corrections | |
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