Elucidation of the mechanism how mutant γPKC causing spinocerebellar ataxia induces neurodegeneration specific to cerebellum.
Project/Area Number |
21700407
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Single-year Grants |
Research Field |
Neurochemistry/Neuropharmacology
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Research Institution | Hiroshima University |
Principal Investigator |
SEKI Takahiro Hiroshima University, 大学院・医歯薬学総合研究科, 助教 (50335650)
|
Project Period (FY) |
2009 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
|
Keywords | 神経・精神疾患の病態と治療 / 脊髄小脳失調症 / プルキンエ細胞 / γPKC / Hsc70 / 脊髄小脳失調症(SCA) / プロテインキナーゼCγ(γPKC) / 小脳プルキンエ細胞 |
Research Abstract |
To elucidate the mechanism how mutant γPKC causing spinocerebellar ataxia induces neurodegeneration specific to cerebella Purkinje cells (PCs), we investigated moleclular properties of mutant γPKC in PCs and in non-PC neurons of cerebellar primary cultures. Compared with non-PC neurons, the mobility of mutant mutant γPKC was prominently reduced in PCs. Moreover, we identified heat shock cognate protein 70 (Hsc70) as a preferable binding protein to mutant γPKC in PCs. These results suggest that mutant γPKC preferably binds to Hsc70 and impairs its functions, leading to PC-selective neurodegeneration.
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Report
(3 results)
Research Products
(58 results)
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[Journal Article] Extracellular ATP differentially modulates Toll-like receptor 4-mediated cell survival and death of microglia.2011
Author(s)
Harada, K., Hide, I., Seki, T., Tanaka, S., Nakata, Y., Sakai, N.
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Journal Title
J.Neurochem. 116
Pages: 1138-1147
Related Report
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[Journal Article] Effect of trehalose on the properties of mutant yPKC, which causes spinocerebellar ataxia type 14,in neuronal cell lines and cultured Purkinje cells.2010
Author(s)
Seki, T., Abe-Seki, N., Kikawada, T., Takahashi, H., Yamamoto, K., Adachi, N., Tanaka, S., Hide, I., Saito, N.and Sakai, N.
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Journal Title
J.Biol.Chem. 285
Pages: 33252-33264
Related Report
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[Journal Article] Congo red, an amyloid-inhibiting compound, alleviates various types of cellular dysfunction triggered by mutant protein kinase Cy that causes spinocerebellar ataxia type 14 (SCA14) by inhibiting oligomerization and aggregation.2010
Author(s)
Seki, T., Takahashi, H., Yamamoto, K., Ogawa, K., Onji, T., Adachi, N., Tanaka, S., Hide, I., Saito, N., Sakai, N.
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Journal Title
J.Pharmacol.Sci. 114
Pages: 206-216
Related Report
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[Journal Article] Mutant protein kinase C gamma that causes spinocerebellar ataxia type 14 (SCA14) is selectively degraded by autophagy.2010
Author(s)
Yamamoto, K., Seki, T., Adachi, N., Takahashi, T., Tanaka, S., Hide, I., Saito, N., Sakai, N.
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Journal Title
Genes Cells 15
Pages: 425-437
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[Journal Article] The C-terminal region of serotonin transporter is important for its trafficking and glycosylation.2009
Author(s)
Nobukuni, M., Mochizuki, H., Okada, S., Kameyama, N., Tanaka, A., Yamamoto, H., Amano, T., Seki, T., Sakai, N.
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Journal Title
J.Pharmacol.Sci. 111
Pages: 392-404
NAID
Related Report
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[Journal Article] Mutant yPKC found in spinocerebellar ataxia type 14 induces aggregate-independent maldevelopment of dendrites in primary cultured Purkinje cells.2009
Author(s)
Seki, T., Shimahara, T., Yamamoto, K., Abe, N., Amano, T., Adachi, N., Takahashi, H., Kashiwagi, K., Saito, N., Sakai, N.
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Journal Title
Neurobiol.Dis. 33
Pages: 260-273
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