2010 Fiscal Year Final Research Report
Clarification of roles of calcium-dependent cytosolic protease calpain on neuronal cell death
| Project/Area Number |
20390030
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
NOBUHISA Iwata The Institute of Physical and Chemical Research, 大学院・医歯薬学総合研究科, 教授 (70246213)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 神経細胞死 / カルシウム依存性プロテアーゼ / カルパイン / カルパスタチン / プロテオミクス / アルツハイマー病 / アミロイドβペプチド / タウ / 小胞膜GABAトランスポーター |
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| Research Abstract |
In this study, I investigated possible involvement of calpain. Using gene-engineering techniques, I generated calpain activity-augmented and suppressed model mice, and clarified that calpain activation caused exacerbation of Aβamyloidosis, tau phosphorylation, microgliosis, somato-dendritic dystrophy and mortality. In addition, I found that vesicular GABA transporter (VGAT) is cleaved by calpain after excitotoxic stimulation or a cerebral ischemia model. These observations indicate that calpain activation may underlie Aβ-triggered pathological cascade and thus shall become a relevant pharmacological target in the treatment of AD.
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[Journal Article] Calpastatin, an endogenous calpain-inhibitor protein, regulates the cleavage of the Cdk5 activator p35 to p25.2011
Author(s)
Ko Sato, Seiji Minegishi, Jiro Takano, Florian Plattner, Taro Saito, Akiko Asada, Hiroyuki Kawahara, Nobuhisa Iwata, Takaomi C.Saido, Shin-ichi Hisanaga.
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Journal Title
J.Neurochem. 117巻
Pages: 504-515
Peer Reviewed
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