Investigation of protein-RNA interaction implicated in neurodegeneration
| Project/Area Number |
15K09822
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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 |
Psychiatric science
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Research Collaborator |
ARAI Tetsuaki 筑波大学, 医学医療系, 教授 (90291145)
AKIYAMA Haruhiko 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 研究員 (20231839)
ISEKI Eizo 順天堂大学, 医学部 (30203061)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 筋萎縮性側索硬化症 / 前頭側頭葉変性症 / TDP-43 / RNA metabolism / 凝集体 / 神経変性 / 神経変性疾患 / 筋委縮性側索硬化症 / FUS / 凝集体形成 / タンパク質凝集体 / RNA代謝 |
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| Outline of Final Research Achievements |
We investigated the effect of truncation of TDP-43 on the expression of poly(A)+ RNA by fluorescence in situ hybridization using HeLa cells transfected with a series of deleted TDP-43 constructs. Endogenous and overexpressed full-length TDP-43 localized to the perichromatin region and interchromatin space adjacent to poly(A)+ RNA. Deleted variants of TDP-43 containing RNA recognition motif 1 and truncating N-terminal region induced cytoplasmic inclusions in which poly(A)+ RNA was recruited. C-terminal TDP-43 truncated at residue 202 or 218 was distributed in the cytoplasm as punctate structures. C-terminal TDP-43 truncated at residue 218 but not at 202 significantly decreased poly(A)+ RNA expression by approximately 24% compared with the level in control cells. Thus, a disturbance of the RNA metabolism in which TDP-43 is involved may be central to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] A family with hereditary diffuse leukoencephalopathy with spheroids caused by a novel c.2442+2T>C mutation in the CSF1R gene.2016
Author(s)
Kawakami I, Iseki E, Kasanuki K, Minegishi M, Sato K, Hino H, Shibuya K, Fujisawa K, Higashi S, Akiyama H, Furuta A, Takanashi M, Li Y, Hattori N, Mitsuyama Y, Arai H.
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Journal Title
Journal of Neuroogicall Science
Volume: 15;367
Pages: 349-55
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Chorea as a clinical feature of the basophilic inclusion body disease subtype of fused-in-sarcoma-associated frontotemporal lobar degeneration.2016
Author(s)
Kawakami I, Kobayashi Z, Arai T, Yokota O, Nonaka T, Aoki N, Niizato K, Oshima K, Higashi S, Katsuse O, Hosokawa M, Hasegawa M, Akiyama H.
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Journal Title
Acta Neuropathol Commun
Volume: 4
Issue: 1
Pages: 36-36
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] 平成27年関東・東北豪雨における常総市水害支援（3）茨城県認知症疾患医療センターの訪問活動.2016
Author(s)
新井 哲明, 安部 秀三, 岡田 正樹, 須磨崎 加寿子, 高濱 浩輔, 田中 芳郎, 山田 武, 高橋 晶, 根本 清貴, 太刀川 弘和, 河合 伸念, 東 晋二, 塚田 恵鯉子, 江湖山 さおり, 堀 孝文
Organizer
第112回日本精神神経学会学術総会
Place of Presentation
千葉県千葉市（幕張メッセ）
Year and Date
2016-06-02
Related Report
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[Presentation] 初診時に緊張病症候群と診断された FTLD-TDP の一例．2016
Author(s)
渡辺亮平, 河上緒, 朝岡俊泰, 大島健一, 新里和弘, 東 晋二, 女屋光基, 新井信隆, 長谷川成人, 秋山治彦, 新井哲明
Organizer
第57回日本神経病理学会総会学術研究会,
Place of Presentation
青森県弘前市（ホテルニューキャッスル）
Year and Date
2016-06-01
Related Report
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