| Project/Area Number |
15K06716
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurophysiology / General neuroscience
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| Research Institution | Jichi Medical University |
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Principal Investigator |
Jimbo Eriko 自治医科大学, 医学部, 講師 (20291651)
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| Co-Investigator(Kenkyū-buntansha) |
桃井 隆 東京医科大学, 医学部, 客員教授 (40143507)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 自閉性スペクトラム障害 / シナプス接着因子 / GPR37 / CADM1 / 自閉性障害 / シナプス接着蛋白遺伝子 |
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| Outline of Final Research Achievements |
In the patients with autism spectrum disorder, mutations of various molecules which exist at synapses, have been found. One of them, GPR37 is included in the G protein coupled receptor. However, little is known about the relation with the disease.In this study, it became clear that GPR37 made each complex of NLGN-PSD95 and CADM1-MUPP1, and bound to scaffold proteins via PDZ binding domain. GPR37 is activated by prosaponin. A short sequence prosapotide can substitute the prosaponin. The signaling via prosaptide was reduced in the neurons of GPR37 deficient mice. GPR37 deficient mice showed slight abnormalities in the number of ultrasound vocalization and waveforms by comparison to wild-type mice. In addition, mutations of GPR37L1,
which is highly homologous to GPR37, were also found in autism.
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| Academic Significance and Societal Importance of the Research Achievements |
自閉性スペクトル障害は近年の社会的な問題であり、治療法の確立が求められているが、発達期の脳は多様な要因に対して影響されるため、分子病態の解明が難しい。本研究では、疾患におけるシナプス接着蛋白質とG蛋白質共役型受容体の複合体形成の異常、シグナル伝達系の異常を明らかにしたところに特徴がある。本研究のような機構解明の足掛かりとなる実験の積み重ねが、患者の社会性行動へ効果や治療にあたり、重要性を持つものと考える。
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