Involvement of TDP-43 and FUS on translational and synaptic control and its relevance to ALS/FTLD
Project/Area Number |
25860708
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Neurology
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Research Institution | Tohoku University (2014-2015) Nagoya University (2013) |
Principal Investigator |
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | ALS/FTLD / シナプス / RNA結合タンパク質 / mRNA代謝 / ALS・FTLD / 転写後遺伝子発現調節 |
Outline of Final Research Achievements |
TDP-43 and FUS are RNA-binding proteins that are involved in neurodegenetive diseases, ALS/FTLD. We demonstrated that FUS knockdown neurons exhibited decreased number of mature synaptic spines and reduced synaptic transmission and that knockdown mice displayed disinhibition and social interaction deficits, reminiscent of FTLD symptoms. On the other hand, TDP-43 knockdown in the mouse hippocampus resulted in long-term memory deficits. Our results indicated that FUS controls the expression of GluA1, a subunit of one of the major glutamate receptors at synapses, by maintaining it mRNA stability. Moreover, behavioral abnormalities of FUS knockdown mice were ameliorated by exogenous expression of GluA1 subunit.
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] FUS regulates AMPA receptor function and FTLD/ALS-associated behaviour via GluA1 mRNA stabilization.2015
Author(s)
Udagawa, T., Fujioka, Y., Tanaka, M., Honda, D., Yokoi, S., Riku, Y., Ibi, D., Nagai, T., Yamada, K., Watanabe, H., Katsuno, M., Inada, T., Ohno, K., Sokabe, M., Okado, H., Ishigaki S*., and Sobue, G.
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Journal Title
Nat Commun
Volume: 6
Issue: 1
Pages: 7098-7098
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] FUS regulates AMPA receptor function and ALS/FTLD-associated behaviors via GluR1 mRNA stabilization2014
Author(s)
Tsuyoshi Udagawa, Yusuke Fujioka, Motoki Tanaka, Daiyu Honda, Satoshi Yokoi, Taku Nagai, Kiyofumi Yamada, Masahisa Katsuno, Masahiro Sokabe, Haruo Okado, Shinsuke Ishigaki, Gen Sobue
Organizer
CSHL meeting 'Translational Control'
Place of Presentation
Cold Spring Harbor
Year and Date
2014-09-02 – 2014-09-06
Related Report
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