Molecular basis of aberrant RNA metabolism in familial ALS type6
| Project/Area Number |
25430080
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Hiroshima Bunkyo Women's University |
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Principal Investigator |
Fujii Ritsuko 広島文教女子大学, 人間科学部, 教授 (90342716)
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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 |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | ALS / FUS/TLS / RNA代謝 / RNA輸送 / D－セリン / リン酸化 / リン酸化シグナル / ＦＵＳ／ＴＬＳ / ＲＮＡ輸送 / ＲＮＡ代謝 |
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| Outline of Final Research Achievements |
Familial amyotrophic lateral sclerosis type6 (FALS6)is caused by aberrant expression of TLS/FUS with ALS-specific point mutations, which leads to intracellular aggregations of the dysfunctional TLS proteins. The protein aggregation of the ALS mutant TLS is not rescued by an expression of wild type TLS. Furthermore, overexpression of ALS mutant TLS does not induce autophagy in spinal cord motor neuron-derived cells, suggesting that pathogenesis of FALS6 is distinct from that of other FALS. Here we show that dysfunctional TLS cannot regulate the expression of Ca2+channel proteins such as specific types of NMDA receptor 1 subunits with high Ca2+ permeability, and also that D-serine content in TLS knockout mouse brains is elevated due to the higher expression of serine racemase. Our findings provide the evidence that motor neurons expressing the mutant TLS responsible for the defective RNA metabolism are susceptible to ALS development.
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Report
(4 results)
Research Products
(5 results)
