Investigation of the role of exosome-mediated maintenance of proteostasis in neurodegenerative diseases.
Project/Area Number |
16H05325
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Osaka University |
Principal Investigator |
Nagai Yoshitaka 大阪大学, 医学系研究科, 寄附講座教授 (60335354)
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Co-Investigator(Kenkyū-buntansha) |
武内 敏秀 大阪大学, 医学系研究科, 寄附講座講師 (70600120)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
|
Keywords | 脳神経疾患 / 認知症 / ストレス / 蛋白質 / 神経科学 / エクソソーム / 分子シャペロン / 痴呆 / タンパク質 |
Outline of Final Research Achievements |
In this study, we investigated the role of exosome-mediated transmission of molecular chaperones on neurodegenerative diseases. We found that expression of molecular chaperones in peripheral tissues non-cell autonomously suppresses eye degeneration of polyglutamine disease model flies. By proteome analyses of blood exosomes of polyglutamine disease model mice and marmosets, we also discovered some biomarker candidates.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、研究代表者および分担者らの独自の知見に基づいて、中枢-末梢連関の視点から神経変性疾患を全身病として捉え、細胞間コミュニケーションの担い手としてエクソソームに着目する点が独創的である。本研究により、エクソソームを介した分子シャペロンの細胞間伝播による生体内プロテオスターシスの維持機構の神経変性疾患病態への関与が明らかになり、エクソソームの補充という新たな視点からの治療法開発への道を拓く。
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Report
(4 results)
Research Products
(164 results)
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[Journal Article] Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid.2019
Author(s)
2. Kakuda K, Ikenaka K, Araki K, So M, Aguirre C, Kajiyama Y, Konaka K, Noi K, Baba K, Tsuda H, Nagano S, Ohmichi T, Nagai Y, Tokuda T, El-Agnaf O, Ogi H, Goto Y, Mochizuki H.
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Journal Title
Sci Rep
Volume: 9
Issue: 1
Pages: 6001-6001
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Arylsulfatase A, a genetic modifier of Parkinson's disease, is an α-synuclein chaperone.2019
Author(s)
J. S. Lee, K. Kanai, M. Suzuki, W. S. Kim, H. S. Yoo, Y. Fu, D-K. Kim, B. C. Jung, M. Choi, K. W. Oh, Y. Li, M. Nakatani, T. Nakazato, S. Sekimoto, M. Furuyama, H. Yoshino, S. Kubo, K. Nishioka, R. Sakai, M. Ueyama, H. Mochizuki, H-J. Lee, S. P. Sardi, G. M. Halliday, Y. Nagai, P. H. Lee, N. Hattori, S-J. Lee
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Journal Title
Brain
Volume: 142
Issue: 9
Pages: 2845-59
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Hippo, Drosophila MST, is a novel modifier of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS.2018
Author(s)
Azuma Y, Tokuda T, Kushimura Y, Yamamoto I, Mizuta I, Mizuno T, Nakagawa M, Ueyama M, Nagai Y, Iwasaki Y, Yoshida M, Pan D, Yoshida H, Yamaguchi M.
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Journal Title
Exp Cell Res.
Volume: 371
Issue: 2
Pages: 311-321
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.2018
Author(s)
Yoshida S, Hasegawa T, Suzuki M, Sugeno N, Kobayashi J, Ueyama M, Fukuda M, Ido-Fujibayashi A, Sekiguchi K, Ezura M, Kikuchi A, Baba T, Takeda A, Mochizuki H, Nagai Y and Aoki M.
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Journal Title
Hum Mol Genet.
Volume: 27
Issue: 5
Pages: 823-836
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Overexpression of ter94, Drosophila VCP, improved motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43.2018
Author(s)
Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
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Journal Title
Am. J. Neurodegener. Dis.
Volume: 7
Pages: 11-31
Related Report
Peer Reviewed
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[Journal Article] A spontaneously immortalized Schwann cell line from aldose reductase-deficient mice as a useful tool for studying polyol pathway and aldehyde metabolism.2018
Author(s)
2.Niimi N, Yako H, Takaku S, Kato H, Matsumoto T, Nishito Y, Watabe K, Ogasawara S, Mizukami H, Yagihashi S, Chung SK, Sango K.
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Journal Title
Journal of Neurochemistry
Volume: 印刷中
Pages: 97-106
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Regulatory Role of RNA Chaperone TDP-43 for RNA Misfolding and Repeat-Associated Translation in SCA312017
Author(s)
Taro Ishiguro, Nozomu Sato, Morio Ueyama, Nobuhiro Fujikake, Chantal Sellier, Akemi Kanegami, Eiichi Tokuda, Bita Zamiri, Terence Gall-Duncan, Mila Mirceta, Yoshiaki Furukawa, 他8名
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Journal Title
Neuron
Volume: 94
Issue: 1
Pages: 108-124
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Transgenic monkey model of the polyglutamine diseases recapitulating progressive neurological symptoms.2017
Author(s)
Tomioka I, Ishibashi H, Minakawa EN, Motohashi HH, Takayama O, Saito Y, Popiel HA, Puentes S, Owari K, Nakatani T, Nogami N, Yamamoto K, Noguchi S, Yonekawa T, Tanaka Y, Fujita N, Suzuki H, Kikuchi H, Aizawa S, Nagano S, Yamada D, Nishino I, Ichinohe N, Wada K, Kohsaka S, Nagai Y, Seki K.
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Journal Title
eNeuro
Volume: 4
Issue: 2
Pages: 0250-56
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Generation of a novel transgenic rat model for tracing extracellular vesicles in body fluids.2016
Author(s)
Yoshimura A, Kawamata M, Yoshioka Y, Katsuda T, Kikuchi H, Nagai Y, Adachi N, Numakawa T, Kunugi H, Ochiya T, Tamai Y.
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 31172-31172
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Regulatory role of RNA chaperone for noncoding repeat RNA aggregation and repeat-associated translation in SCA31.2017
Author(s)
Nagai Y., Ishiguro T., Sato N., Ueyama M., Fujikake N., Yokota T., Wada K., Mizusawa H., Ishikawa K.
Organizer
The 43rd Naito Conference on Noncoding RNA:Biology, Chemistry, & Diseases
Related Report
Int'l Joint Research
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[Presentation] Transgenic monkey model of the polyglutamine diseases recapitulating progressive neurological symptoms and polyglutamine protein inclusions.2017
Author(s)
Nagai Y., Tomioka I., Ishibashi H., Minakawa E.N, Motohashi H.H., Takayama O., Saito Y., Popiel H.A., Puentes S., Owari K., Nakatani T., Nogami N., Yamamoto K., Noguchi S., Nagano S., Nishino I., Ichinohe N., Wada K., Kohsaka S., Seki K.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Related Report
Int'l Joint Research
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[Presentation] Balance between RNA binding proetin TDP-43 and an RNA UGGAA repeat underlies pathogenesis of spinocerebellar ataxia type 31 (SCA31) and motor neuron disease fly models.2017
Author(s)
13.Ishiguro T., Sato N., Ueyama M., Fujikake N., Sellier C., Tokuda E., Zamiri B., Gall-Duncan T., Mirceta M., Furukawa Y., Yokota T., Wada K., Taylor J.P., Pearson C.E., Charlet-Berguerand N., Mizusawa H., Nagai Y., Ishikawa K.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Related Report
Int'l Joint Research
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[Presentation] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.2017
Author(s)
Hasegawa T., Yoshida S., Suzuki M., Sugeno N., Kobayashi J., Ueyama M., Ezura M., Kikuchi A., Baba T., Takeda A., Mochizuki H., Nagai Y., Aoki M.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Related Report
Int'l Joint Research
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[Presentation] The search for genes that modulate FUS-mediated phenotypes by Drosophila amyotrophic lateral sclerosis model.2017
Author(s)
Azuma Y., Tokuda T., Kushimura Y., Yamamoto I., Yoshida H., Mizuta I., Ueyama M., Nagai Y., Nakagawa M., Mizuno T., Yamaguchi M.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Related Report
Int'l Joint Research
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[Presentation] Loss of function mutant of ter94, Drosophila VCP, partially enhanced motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43.2017
Author(s)
Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Yoshida H., Mizuta I., Ueyama M., Nagai Y., Nakagawa M., Mizuno T., Yamaguchi M.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Related Report
Int'l Joint Research
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[Presentation] The search for genes that modulate FUS-mediated phenotypes by Drosophila amyotrophic lateral sclerosis model.2017
Author(s)
Azuma Y., Tokuda T., Kushimura Y., Yamamoto I., Ueoka I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
Organizer
CSHL 2017 Neurobiology of Drosophila
Related Report
Int'l Joint Research
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[Presentation] Loss of function mutant of ter94, Drosophila VCP, partially enhanced motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43.2017
Author(s)
Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Ueoka I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
Organizer
CSHL 2017 Neurobiology of Drosophila
Related Report
Int'l Joint Research
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[Presentation] Regulatory role of RNA chaperone TDP-43 for RNA misfolding and repeat-associated translation in SCA31.2017
Author(s)
Ishikawa K., Ishiguro T., Sato N., Ueyama M., Fujikake N., Sellier C., Tokuda E., Zamiri B., Gall-Duncan T., Mirceta M., Furukawa Y., Yokota T., Wada K., Taylor J.P., Pearson C.E., Charlet-Berguerand N., Mizusawa H., Nagai Y.
Organizer
67th Annual Meeting of American Society of Human Genetics
Related Report
Int'l Joint Research
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[Presentation] Toxicity of dipeptide repeat proteins in C9 ALS/FTD model fly.2016
Author(s)
Ueyama M., Ishiguro T., Gendron T.F., Fujikake N., Konno T., Koyama A., Onodera O., Ishikawa K., Wada K., Petrucelli L., Nagai Y.
Organizer
4th RNA Metabolism in Neurological Disease Conference
Related Report
Int'l Joint Research
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