| Project/Area Number |
25293061
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Hiroshima University |
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Principal Investigator |
Sakai Norio 広島大学, 医歯薬保健学研究院, 教授 (70263407)
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| Co-Investigator(Kenkyū-buntansha) |
HIDE IZUMI 広島大学, 医歯薬保健学研究院, 助教 (20253073)
TANAKA SHIGERU 広島大学, 医歯薬保健学研究院, 助教 (20512651)
MORINOBU SHIGERU 広島大学, 医歯薬保健学研究院, 特任教授 (30191042)
SHIRAFUJI TOSHIHIKO 広島大学, 医歯薬保健学研究院, 助教 (30595765)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | protein kinase C / serotonin transporter / GPCR / microglia / neurite outgrowth / neurodegeneration / macropinocytosis / heat shock protein / 神経変性疾患 / アミロイド凝集 / Gタンパク質共役受容体 / 神経突起伸長 / ミクログリア / 小胞体関連分解 / セロトニントランスポーター / 膜輸送 / オートファジー / 脳虚血 / うつ病 |
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| Outline of Final Research Achievements |
In this study, we intend to develop novel strategies to treat intractable neuropsychiatric disease, including neurodegenerative disease, ischemic brain disease and mood disorders. For this purpose, we focused on the impairment of protein membrane trafficking and degradation as a common mechanism underlying the pathogenesis of these disease. Regarding the neurodegenerative disease, we analyzed mutant gamma PKC, which causes spinocerebellar ataxia type 14 (SCA14). We clarified that mutant gamma PKC formed amyloid fibril and prevented macropinocytosis. G-protein-coupled receptor 3 (GPR3), a therapeutic target of ischemic brain disease, was found to move to the tip of neurite, and to regulate neurite outgrowth. Furthermore, we identified that ligands of sigma 1 receptor could up-regulate the function of serotonin transporter, a target of antidepressant, by facilitating its membrane trafficking.
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