2002 Fiscal Year Final Research Report Summary
A study on the mechanism of α-synuclein deposition: Is a novel α-synuclein interacting protein involved in α-synucleinopathies?
| Project/Area Number |
13670682
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | National Institute of Neuroscience, NCNP |
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Principal Investigator |
ARAKI Wataru Dept. Demyelinating Dis. &Aging Chief, 疾病研究第6部, 室長 (60311429)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Keikichi Dept. Demyelinating Dis. &Aging Chief, 疾病研究第6部, 室長 (40117148)
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| Project Period (FY) |
2001 – 2002
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| Keywords | α-synuclein / neurodegenerative disorder |
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| Research Abstract |
Deposition of α-synuclein (α-Syn) in Lewy bodies is a pathological hallmark of several neurodegerative disorders, including Parkinson's disease and dementia with Lewy bodies, and this abnormal deposition of α-Syn appears to be associated with neurodegeneration. Based on the hypothesis that any protein interacting with α-Syn may play a role in the mechanism of α-Syn deposition, we searched for proteins physically interacting with α-Syn, using yeast two-hybrid screening. We obtained one positive clone which corresponds to a partial cDNA of an unknown gene. Subsequent screening of a human brain cDNA library and EST data base searches yielded full-length cDNA clones. We named this novel gene αSNBP (α-synuclein binding protein). This gene encodes a protein consisting of 463 amino acids. Northern blot analysis showed that αSNBP mRNA is expressed in multiple tissues including brain. Western blot analysis of αSNBP-transfected cells showed that αSNBP is expressed as a protein of 〜60 kD. Co-immunoprecipitation analysis of a soluble fraction from cells co-expressing α-Syn and αSNBP indicated binding of these proteins. Immunofluorescence staining of the cells also suggested co-localization of the two proteins. Immunohistochemical staining of human brain specimens with a specific αSNBP antibody showed that αSNBP is expressed in neurons at variable levels.
We conclude that αSNBP is a novel protein physically interacting with α-Syn. Further investigation concerning whether αSNBP is involved in the neuropathology of α-synucleinopathies is in progress.
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