Adult neurogenesis in the mouse models of ALS/FTLD
Project/Area Number |
15K09310
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Nagoya University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
渡辺 宏久 名古屋大学, 脳とこころの研究センター, 特任教授 (10378177)
祖父江 元 名古屋大学, 医学系研究科, 特任教授 (20148315)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | Adult neurogenesis / FTLD / ALS / tau / FUS / SFPQ / adult neurogenesis / 前頭側頭葉変性症 / タウ / 成体神経新生 |
Outline of Final Research Achievements |
Fused in sarcoma (FUS) and splicing factor, proline- and glutamine-rich (SFPQ) are RNA binding proteins that regulate RNA metabolism. We found that alternative splicing of the Mapt gene at exon 10, which generates 4-repeat tau (4R-T) and 3-repeat tau (3R-T), is regulated by interactions between FUS and SFPQ in the nuclei of neurons. Hippocampus-specific FUS- or SFPQ-knockdown mice exhibit frontotemporal lobar degeneration (FTLD)-like behaviors, reduced adult neurogenesis, accumulation of phosphorylated tau, and hippocampal atrophy with neuronal loss through an increased 4R-T/3R-T ratio. Normalization of this increased ratio by 4R-T specific silencing resulted in recovery of the normal phenotype. These findings suggest a biological link among FUS/SFPQ, tau isoform alteration, and phenotypic expression, which may function in the early pathomechanism of ALS/FTLD.
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Report
(4 results)
Research Products
(49 results)
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[Journal Article] Silencing of FUS in the common marmoset (Callithrix jacchus) brainvia stereotaxic injection of an adeno-associated virus encoding shRNA.2018
Author(s)
Endo K, Ishigaki S, Masamizu Y, Fujioka Y, Watakabe A, Yamamori T, Hatanaka N, Nambu A, Okado H, Katsuno M, Watanabe H, Matsuzaki M, Sobue G
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Journal Title
Neurosci Res
Volume: in press
Pages: 30183-9
DOI
Related Report
Peer Reviewed
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[Journal Article] Altered tau isoform ratio caused by loss of Fus and Sfpq function leads to FTLD-like phenotypes2017
Author(s)
Ishigaki S, Fujioka Y, Okada Y, Riku Y, Udagawa T, Honda D, Yokoi S, Endo K, Ikenaka K, Takagi S, Iguchi Y, Sahara N, Takashima A, Okano H, Yoshida M, Warita H, Aoki M, Watanabe H, Okado H, Katsuno H, Sobue G.
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Journal Title
Cell Reports
Volume: 18
Issue: 5
Pages: 1118-1131
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Gene Expression Profile of Inflammatory Myopathy with Malignancy is Similar to that of Dermatomyositis rather than Polymyositis2016
Author(s)
Noda, T., Iijima, M., Noda, S., Maeshima, S., Nakanishi, H., Kimura, S., Koike, H., Ishigaki, S., Iguchi, Y., Katsuno, M., and Sobue, G.
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Journal Title
Internal Medicine
Volume: 55
Issue: 18
Pages: 2571-2580
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed
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[Journal Article] Involvement of the caudate nucleus head and its networks in sporadic amyotrophic lateral sclerosis-frontotemporal dementia continuum.2016
Author(s)
Masuda, M., Senda, J., Watanabe, H., Epifanio, B., Tanaka, Y., Imai, K., Riku, Y., Li, Y., Nakamura, R., Ito, M., Ishigaki, S., Atsuta, N., Koike, H., Katsuno, M., Hattori, N., Naganawa, S., and Sobue, G.
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Journal Title
Amyotroph Lateral Scler Frontotemporal Degener
Volume: 17
Pages: 571-579
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] R-spondin 2 promotes acetylcholine receptor clustering at the neuromuscular junction via Lgr5.2016
Author(s)
Nakashima H., Ohkawara B., Ishigaki S., Fukudome T., Ito K., Tsushima M., Konishi H., Okuno T., Yoshimura T., Ito M., Masuda A., Sobue G., Kiyama H., Ishiguro N., Ohno K.
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Journal Title
Sci Rep
Volume: 22
Issue: 1
Pages: 28512-28512
DOI
Related Report
Peer Reviewed / Open Access
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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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[Journal Article] Transcriptional and post-transcriptional regulation of transmembrane protein 132A.2015
Author(s)
Oh-Hashi, K., Sone, A., Hikiji, T., Hirata, Y., Vitiello, M., Fedele, M., Ishigaki S., Sobue, G., and Kiuchi, K.
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Journal Title
Mol Cell Biochem
Volume: 405
Issue: 1-2
Pages: 291-299
DOI
Related Report
Peer Reviewed
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[Journal Article] A highly sensitive assay of IRE1 activity using the small luciferase NanoLuc: Evaluation of ALS-related genetic and pathological factors.2015
Author(s)
Hikiji, T., Norisada, J., Hirata, Y., Okuda, K., Nagasawa, H., Ishigaki S., Sobue, G., Kiuchi, K., and Oh-hashi, K.
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Journal Title
Biochem Biophys Res Commun
Volume: 463
Issue: 4
Pages: 881-887
DOI
Related Report
Peer Reviewed
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[Presentation] Accumulation of phosphorylated tau in neurons in FUS-silenced mice.2016
Author(s)
27.Ishigaki S, Fujioka Y, Honda D, Yokoi S, Endo K., Okado H, Watanabe H, Katsuno M, Takashima A., Sobue G.
Organizer
The 46th Society for Neuroscience annual meeting
Place of Presentation
San Diego, USA
Year and Date
2016-11-12
Related Report
Int'l Joint Research
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[Presentation] Loss of FUS causes a decrease in brain volume accompanied with neuronal loss2015
Author(s)
Fujioka Y, Ishigaki S, Yokoi S, Honda D, Udagawa T, Okado H, Yoshikawa M, Takashima A, Watanabe H, Katsuno M, Sobue G.
Organizer
The 45th Society for Neuroscience annual meeting
Place of Presentation
Chicago, IL USA
Year and Date
2015-10-17
Related Report
Int'l Joint Research
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[Presentation] Loss of FUS causes a decrease in brain volume accompanied with neuronal loss2015
Author(s)
Fujioka Y, Ishigaki S, Yokoi S, Honda D, Udagawa T, Okado H, Yoshikawa M, Takashima A, Watanabe H, Katsuno M, Sobue G.
Organizer
The 10th brain research conference
Place of Presentation
Chicago, IL USA
Year and Date
2015-10-15
Related Report
Int'l Joint Research
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[Presentation] FUS regulates AMPA receptor function and FTLD/ALS-associated behavior via GluA1 mRNA stabilization2015
Author(s)
Honda D, Udagawa T, Fujioka Y, Tanaka M, Yokoi S, Nagai T, Yamada K, Ishigaki S, Watanabe H, Katsuno M, Ohno K, Sokabe M, Okado H, Sobue G.
Organizer
The 38th annual Meeting of the Japan Neuroscience Society
Place of Presentation
兵庫県 神戸市 神戸国際会議場
Year and Date
2015-07-28
Related Report
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