2015 Fiscal Year Final Research Report
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 |
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| Research Field |
Neurology
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| Research Institution | Tohoku University (2014-2015)
Nagoya University (2013) |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | ALS/FTLD / シナプス / RNA結合タンパク質 / mRNA代謝 |
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| 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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| Free Research Field |
分子神経科学
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