Identification of therapeutic targets for ALS by screening for TDP-43 and FUS associated molecules
| Project/Area Number |
23659452
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Nagoya University |
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Principal Investigator |
SOBUE Gen 名古屋大学, 医学系研究科, 教授 (20148315)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 筋萎縮性側索硬化症 / ALS / FUS / 小胞体ストレス / 改変GFP / 検知システム / 神経変性疾患モデル細胞 |
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| Research Abstract |
Mouse primary cortical neurons were silenced with FUS by introducing lentivirus encoding shRNA against FUS gene. We next established the FUS-regulated transcriptome profiles of primary neurons using exon-sensitive microarrays and identified that FUS regulated the alternative splicing of Mapt exon10. This alternative splicing event results in three-repeats (RD3) and four-repeats (RD4) Tau isoform production and the ratio of RD4/RD3 was increased when FUS was silenced in neurons. Morphological abnormality of neurite was observed in FUS-silenced primary neurons and it was rescued bysilencing of RD4. These findings suggest that RD4 could be a therapeutic target for ALS treatment.
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] Loss of TDP-43 causes age-dependent progressive motor neuron degeneration2013
Author(s)
Iguchi Y, Katsuno M, Niwa JI, Takagi S, Ishigaki S, Ikenaka K, Kawai K, Watanabe H, Yamanaka K, Takahashi R, Misawa H, Sasaki S, Tanaka F, Sobue G
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Journal Title
Related Report
Peer Reviewed
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