| Project/Area Number |
22300121
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Nagasaki University |
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Principal Investigator |
MORI Nozomu 長崎大学, 医歯(薬)学総合研究科, 教授 (00130394)
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| Co-Investigator(Kenkyū-buntansha) |
MASAHIKO Sibazaki 長崎大学, 医歯薬学総合研究科, 助教 (20445109)
SHO Kakizawa 長崎大学, 医歯薬学総合研究科, 講師 (40291059)
KYOJI Ohyama 長崎大学, 医歯薬学総合研究科, 准教授 (00255423)
KUNIHIKO Yasuda 長崎大学, 医歯薬学総合研究科, 助教 (50278446)
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| Co-Investigator(Renkei-kenkyūsha) |
YOKO Hiraishi-yamaguchi 長崎大学, 先導生命研究センター (50311345)
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| Project Period (FY) |
2010-04-01 – 2013-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2012: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2010: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | 老化 / 寿命 / 脳 / 神経可塑性 / シグナル伝達 / 蛋白質凝集 / アセチル化 / 神経 / 可塑性 / オートファジー / 微小管 / 蛋白凝集 |
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| Research Abstract |
While we explored functional deficits in the newly made N-Shc and Grit/RICS double KO mice, we were unable to define a specific phenotype. However, in ShcB deficient mice, we found a unique change in cerebellar-dependent motor learning, which was associated with reduced long-term depression as well as a deficit in calcium release from the endoplasmic reticulum store of Purkinje cells. We also examined a potential role of Mdm20, an auxiliary subunit of protein N-terminal acetyl transferase, and found that Mdm20 promotes polyQ aggregation via inhibiting autophagy through affecting serine-473 phosphorylation of AKT, an upstream kinase in the regulation of cytoplasmic proteostasis. These results suggest that neural enriched ShcB and Mdm20 play independent roles in neuronal synaptic plasticity and proteostasis, respectively.
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