2017 Fiscal Year Final Research Report
Mechanistic investigation and new therapeutic development for West syndrome
| Project/Area Number |
25293239
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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 |
Pediatrics
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
YAMAGATA Kanato 公益財団法人東京都医学総合研究所, 脳発達・神経再生研究分野, 分野長 (20263262)
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| Co-Investigator(Kenkyū-buntansha) |
藤原 浩樹 山形大学, 医学部, 助教 (50433868)
田中 秀和 立命館大学, 生命科学部, 教授 (70273638)
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| Co-Investigator(Renkei-kenkyūsha) |
KATSURABAYASHI Shutaro 福岡大学, 薬学部, 准教授 (50435145)
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| Project Period (FY) |
2013-04-01 – 2018-03-31
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| Keywords | West症候群 |
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| Outline of Final Research Achievements |
To elucidate the mechanism for West syndrome, we investigated the pathogenesis of tuberous sclerosis complex (TSC), which is one of the causes of this syndrome. We have clarified a novel mechanism that Rheb activation, but not mTORC1, increases syntenin levels, which impairs dendritic spine morphology. Therefore, we reduced syntenin levels in TSC model mice, resulting in recovery of spine morphology and memory disorder. Next, to generate TSC model mice with spontaneous seizures, we deleted Tsc1 gene in the specific neurons or glial cells. We found some mice showed epilepsy and impaired memory. Finally, we found pharmacological inhibition of Rheb is effective for the symptoms of neuron- and glia-specific Tsc1 knockout mice.
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| Free Research Field |
神経薬理学
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