Establishment of cellular and rodent models for amyotrophic lateral sclerosis using recombinant viral vectors
Project/Area Number |
24500428
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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 |
Nerve anatomy/Neuropathology
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Research Institution | Tokyo Metropolitan Institute of Medical Science |
Principal Investigator |
WATABE Kazuhiko 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 副参事研究員 (30240477)
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Project Period (FY) |
2012-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 運動ニューロン / TDP-43 / FUS / 筋萎縮性側索硬化症 / 凝集体 / 組換えウイルス / プロテアソーム / オートファジー / アデノウイルス / ESCRT |
Outline of Final Research Achievements |
Formation of TDP-43- or FUS-positive cytoplasmic aggregates in neuronal and glial cells is one of the pathological hallmarks of amyotrophic lateral sclerosis (ALS). We have demonstrated that inhibition of protein degradation pathways enhanced adenovirus-induced neuronal cytoplasmic aggregate formation of TDP-43 and FUS in vitro and in vivo. We then produced recombinant adeno-associated virus type 9 (AAV9) and lentivirus vectors encoding wild type and mutant TDP-43 or FUS, and those encoding shRNAs for protein degradation machineries and demonstrated their long-term retrograde transduction of the foreign genes and formation of cytoplasmic aggregates in adult mouse facial and spinal motoneurons. We also performed time-lapse imaging analysis of neuronal and glial cells infected with adenoviruses encoding TDP-43 and FUS cDNAs under conditions of proteasome inhibition to examine cytoplasmic aggregate formation, cell death, and cell to cell spreading of these aggregates.
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Report
(5 results)
Research Products
(67 results)
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[Journal Article] Schwann cells contribute to neurodegeneration of transthyretin amyloidosis2015
Author(s)
Murakami, T., Sango, K., Watabe, K., Niimi, N., Takaku, S., Li, Z, Yamamura, K., Sunada, Y.
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Journal Title
J. Neurochem
Volume: 134
Issue: 1
Pages: 66-74
DOI
Description
in press
Related Report
Peer Reviewed
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[Journal Article] Predictors of impaired communication in amyotrophic lateral sclerosis patients with tracheostomy invasive ventilation2015
Author(s)
Nakayama Y, Shimizu T, Mochizuki Y, Hayashi Y, Matsuda C, Nagao M, Watabe K, Kawata A, Oyanagi K, Isozaki E, Nakano I
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Journal Title
Amyotroph Lateral Scler Frontotemporal Degener
Volume: 未
Issue: 1-2
Pages: 38-46
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] SIMPLE, a causative gene for Charcot-Marie-Tooth disease type 1C, participates in protein trafficking in trans-Golgi network and recycling endosome.2015
Author(s)
Moriwaki Y, Ohno Y, Ishii T, Takamura Y, Sango K, Watabe K, Misawa H.
Organizer
45th Annual Meeting of Society for Neuroscience
Place of Presentation
Chicago, IL, USA
Year and Date
2015-10-17
Related Report
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[Presentation] Phase numbers and duration of fasciculation potentials (FPs) have negative correlation with muscle strength in ALS patients---A quantitative analysis-.2014
Author(s)
Bokuda K, Shimizu T, Kimura H, Yamazaki T, Sekiguchi T, Kamiyama T, Watabe K, Kawata A, Tanaka K, Nakano I.
Organizer
25th International Symposium on ALS/MND
Place of Presentation
Brussels, Belgium
Year and Date
2014-12-06
Related Report
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[Presentation] Schwann cell biology and pathology.2014
Author(s)
Watabe K.
Organizer
Brain Conference 2014, the Joint Conference of Congress of Asian Society of Neuropathology, Korean Society for Brain and Neural Science, and Korean Society for Neurodegenerative Diseases.
Place of Presentation
Seoul, Korea.
Year and Date
2014-11-06
Related Report
Invited
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[Presentation] Myelination in coculture of rodent stem cell-derived neurons and Schwann cell lines.2014
Author(s)
Watabe K, Ishii T, Yanagisawa H, Sango K, Akiyama K, Kawakami E, Endo K, Tsukamoto M, Niimi N, Akutsu H, Misawa H.
Organizer
XVIIIth International Congress of Neuropathology
Place of Presentation
Rio de Janeiro, Brazil
Year and Date
2014-09-17
Related Report
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[Presentation] Retrograde axonal delivery of TDP-43 and FUS genes using AAV9 and lentivirus vectors to adult mouse motoneurons.2014
Author(s)
Ishii T, Akiyama K, Kawakami E, Yanagisawa H, Sango K, Okado H, Miwa A, Miyake K, Kato S, Kobayashi K, Misawa H, Watabe K.
Organizer
XVIIIth International Congress of Neuropathology
Place of Presentation
Rio de Janeiro, Brazil
Year and Date
2014-09-15
Related Report
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