A gain of toxic function hypothesis via accumulated RNA-binding protein and repeat RNA in the pathogenesis of ALS and its validation in vivo
| Project/Area Number |
24659438
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | 独立行政法人国立精神・神経医療研究センター |
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Principal Investigator |
NAGAI Yoshitaka 独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第四部, 室長 (60335354)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 遺伝子 / 神経科学 / 蛋白質 / 脳神経疾患 / RNA / ALS / リピートRNA / RNA結合蛋白質 |
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| Research Abstract |
Based on the hypothesis that abnormal accumulation of RNA would trigger aggregation and accumulation of the RNA-binding proteins, eventually leading to neurodegeneration in the pathogenesis of amyotrophic lateral sclerosis (ALS), 1) we established novel ALS model flies expressing expanded GGGGCC repeat RNA, which mimic neurological phenotypes and pathology of human ALS patients. 2) Furthermore, using this newly-established ALS models flies, we have successfully identified some RNA-binding proteins that can modify the toxicity of expanded GGGGCC repeat RNA in vivo. We therefore conclude that RNA-binding proteins are involved in neurotoxicity of abnormal RNA accumulation, which can contribute to the pathomechanism of ALS.
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Report
(3 results)
Research Products
(75 results)
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[Journal Article] Identification of ter94, Drosophila VCP, as a strong modulator of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS2014
Author(s)
Azuma Y., Tokuda T., Shimamura M., Kyotani A., Sasayama H., Yoshida T., Mizuta I., Mizuno T., Nakagawa M., Fujikake N., Ueyama M., Nagai Y., Yamaguchi M
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Journal Title
Hum. Mol. Genet
Volume: 23(13)
Issue: 13
Pages: 3467-3480
DOI
Related Report
Peer Reviewed
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[Journal Article] Knockdown of the Drosophila Fused in Sarcoma (FUS) homologue causes deficient locomotive behavior and shortening of motoneuron terminal branches.2012
Author(s)
Sasayama, H., Shimamura, M., Tokuda, T., Azuma, Y., Yoshida, T., Mizuno, T., Nakagawa, M., Fujikake, N., Nagai, Y. and Yamaguchi, M
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Journal Title
PLoS ONE
Volume: 7(6),
Issue: 6
Pages: e39483-e39483
DOI
Related Report
Peer Reviewed
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[Presentation] Identification of a polyglutamine oligomerization inhibitor with high brain permeability and safety, which exerts therapeutic effects on multiple mouse models of the polyQ diseases.2013
Author(s)
Popiel H.A., Yamane H., Takahashi T., Tada M., Saitoh Y., Fujita H., Okamoto Y., Toda T., Wada K., Onodera O., Nagai Y.
Organizer
7th Gordon Research Conference on CAG Triplet Repeat Disorders
Place of Presentation
Waterville Valley, NH
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