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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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | West症候群 / てんかん / 難治性てんかん |
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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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Report
(6 results)
Research Products
(47 results)
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[Journal Article] Glucose-dependent acetylation of Rictor promotes targeted cancer therapy resistance.2015
Author(s)
Masui K, Tanaka K, Ikegami S, Villa GR, Yang H, Yong WH, Cloughesy TF, Yamagata K, Arai N, Cavenee WK, Mischel PS.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 112(30)
Issue: 30
Pages: 9406-9411
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Activation of Rheb, but not of mTORC1, impairs spine synapse morphogenesis in tuberous sclerosis complex.2014
Author(s)
Yasuda S, Sugiura H, Katsurabayashi S, Shimada T, Tanaka H, Takasaki K, Iwasaki K, Kobayashi T, Hino O, Yamagata K.
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Journal Title
Sci Rep.
Volume: 4
Issue: 1
Pages: 5155-5155
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Rheb activation disrupts spine synapse formation through accumulation of syntenin in tuberous sclerosis complex2015
Author(s)
Yasuda S, Sugiura H, Katsurabayashi S, Kawano H, Endo K, Takasaki K, Iwasaki K, Ichikawa M, Kobayashi T, Hino O, Yamagata K
Organizer
第58回日本神経化学会大会
Place of Presentation
大宮ソニックシティ（埼玉県さいたま市）
Year and Date
2015-09-12
Related Report
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[Presentation] Activation of Rheb, but not of mTORC1, impairs spine synapse morphogenesis in tuberous sclerosis complex.2014
Author(s)
Yasuda S, Sugiura H, Katsurabayashi S, Shimada T, Tanaka H, Takasaki K, Iwasaki K, Kobayashi T, Hino O, Yamagata K
Organizer
第３６回日本生物学的精神医学会・第５７回日本神経化学会大会合同年会
Place of Presentation
奈良県文化会館（奈良県奈良市）
Year and Date
2014-09-29 – 2014-10-01
Related Report
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