The mechanism of cytotoxicity from ALS-linked Profilin 1 mutations
Project/Area Number |
15K18370
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Nerve anatomy/Neuropathology
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Research Institution | Tokyo Metropolitan Institute of Medical Science |
Principal Investigator |
TANAKA Yoshinori 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 (00747933)
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Co-Investigator(Renkei-kenkyūsha) |
HASEGAWA Masato 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, 分野長 (10251232)
NONAKA Takashi 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, 副参事研究員 (30356258)
KAMETANI Fuyuki 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, 主席研究員 (70186013)
SUZUKI Genjiro 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, 主席研究員 (60466034)
HOSOKAWA Masato 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, 主席研究員 (00435116)
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Project Period (FY) |
2015-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | Profilin1 / TDP-43 / ALS / mutation / aggresome / LC3 / seeding / prion / プロフィリン1 / アグリソーム / 筋萎縮性側索硬化症 / プリオン |
Outline of Final Research Achievements |
The nuclear protein TDP-43 accumulates at the cytoplasm of motor neurons, as a pathological form, in the patients of amyotrophic lateral sclerosis (ALS). As the role of TDP-43 in the nucleus is essential, the accumulation of pathological TDP-43 is identified as a cause of ALS. In the present study, we investigated the effect of ALS-linked PFN1 gene mutations, a cause of familial ALS characteristic of TDP-43 accumulation, on the accumulation of TDP-43 using cultured cells. The cells expressing mutant PFN1 harbored PFN1 aggregates, and those sequestered TDP-43. Furthermore, TDP-43 sequestered into PFN1 aggregates was partly converted into the pathological form of TDP-43 that promotes TDP-43 accumulation like a pathological prion.
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Report
(3 results)
Research Products
(18 results)
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[Journal Article] Phosphorylation of TAR DNA-binding Protein of 43 kDa (TDP-43) by Truncated Casein Kinase 1δ Triggers Mislocalization and Accumulation of TDP-43.2016
Author(s)
Nonaka T, Suzuki G, Tanaka Y, Kametani F, Hirai S, Okado H, Miyashita T, Saitoe M, Akiyama H, Masai H, Hasegawa M.
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Journal Title
The journal of Biological Chemistry
Volume: 291
Issue: 11
Pages: 5473-83
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Progranulin mediates neurovascular protection via multiple therapeutic effects in experimental acute ischemic stroke.2015
Author(s)
Kanazawa M, Kawamura K, Takahashi T, Miura M, Tanaka Y, Koyama M, Toriyabe M, Igarashi H, Nakada T, Nishihara M, Nishizawa M, Shimohata T.
Organizer
Brain and Brain PET 2015
Place of Presentation
バンクーバー(カナダ)
Year and Date
2015-06-27
Related Report
Int'l Joint Research
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