Development of screening methods to find novel therapeutic drugs for neurodegenerative disease using fluorescence-based probe and high-content microscope.
| Project/Area Number |
24659117
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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 |
General pharmacology
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| Research Institution | Hiroshima University |
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Principal Investigator |
SAKAI NORIO 広島大学, 医歯薬保健学研究院, 教授 (70263407)
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| Co-Investigator(Kenkyū-buntansha) |
SEKI Takahiro 熊本大学, 生命科学研究部, 准教授 (50335650)
HIDE Izumi 広島大学, 大学院医歯薬保健学研究院, 助教 (20253073)
TANAKA Shigeru 広島大学, 大学院医歯薬保健学研究院, 助教 (20512651)
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 神経変性疾患 / タンパク質分解 / イメージング / タンパク質リン酸化酵素 / ケミカルシャペロン / 膜輸送 / セロトニントランスポーター / 脳虚血 / うつ病 / マクロピノサイトーシス / セロトニントラスポーター |
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| Research Abstract |
1. We developed novel fluorescence-based probe that can access the activity of chaperone-mediated autophagy (CMA) in a single cell level. Using this probe, we identified the decreased level of CMA in a cellular model of spinocerebellar ataxia type 14 (SCA14), indicating that CMA is a novel therapeutic target for neurodegenerative disease.
2.Imaging analysis using SCA14 mutant gamma PKC,-GFP elucidated that HSP70, a member of molecular chaperone, is involved in the compensation of cytotoxicity induced by SCA14 mutant gamma PKC.
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Report
(3 results)
Research Products
(68 results)
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[Journal Article] The role of Pak-Interacting Exchange Factor-13 phosphorylation at Serine 340 and 583 by PKCy in the dopamine release2014
Author(s)
Shirafuji, T., Ueyama, T., Yoshino, K., Takahashi, H., Adachi, N., Ago, Y., Koda, K., Nashida, T., Hiramatsu, N., Matsuda, T., Toda, T., Sakai, N. and Saito, N.
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Journal Title
J. Neuroscience.
Volume: (In press)
Related Report
Peer Reviewed
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[Journal Article] Selective blockade of N-methyl-D-aspartate channels in combination with dopamine receptor antagonism induces loss of the righting reflex in mice, but not immobility2014
Author(s)
Kikuchi, N., Irifune, M., Shimizu, Y., Yoshida, K., Morita, K., Kanematsu, T., Morioka, N., Nakata, Y., Sakai, N.
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Journal Title
Psychopharmacology
Volume: (In press)
Related Report
Peer Reviewed
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[Journal Article] A brain-specific Grb2-associated regulator of extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) (GAREM) subtype, GAREM2, contributes to neurite outgrowth of neuroblastoma cells by regulating Erk signaling.2013
Author(s)
Taniguchi T, Tanaka S, Ishii A, Watanabe M, Fujitani N, Sugeo A, Gotoh S, Ohta T, Hiyoshi M, Matsuzaki H, Sakai N, Konishi H.
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Journal Title
J Biol Chem.
Volume: 288
Issue: 41
Pages: 29934-29942
DOI
Related Report
Peer Reviewed
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[Journal Article] Mutant gammaPKC that causes spinocerebellar ataxia type 14 upregulates Hsp70, which protects cells from the mutant's cytotoxicity.2013
Author(s)
Ogawa, K., Seki, T., Onji, T., Adachi, N., Tanaka, S., Hide, I., Saito, N., Sakai, N.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 440
Issue: 1
Pages: 25-30
DOI
Related Report
Peer Reviewed
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[Journal Article] JosD1, a membrane-targeted deubiquitinating enzyme, is activated by ubiquitination and regulates membrane dynamics, cell motility and endocytosis.2013
Author(s)
Seki, T., Gong, J., Williams, A. J., Sakai, N., Todi, S. V. and Paulson, H. L.
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Journal Title
J. Biol. Chem.
Volume: 288
Issue: 24
Pages: 17145-17155
DOI
Related Report
Peer Reviewed
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[Journal Article] Effects of the Chemical Chaperone 4-Phenylbutylate on the Function of the Serotonin Transporter (SERT) Expressed in COS-7 Cells2013
Author(s)
Fujiwara, M., Yamamoto, H., Miyagi, T., Seki, T., Tanaka, S., Hide, I., Sakai, N.
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Journal Title
Journal of Pharmacological Sciences
Volume: 122
Issue: 2
Pages: 71-83
DOI
NAID
ISSN
1347-8613, 1347-8648
Related Report
Peer Reviewed
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[Journal Article] Effects of the chemical chaperone 4-phenylbutylate on the function of the serotonin transporter (SERT) expressed in COS-7 cells.2013
Author(s)
Fujiwara, M., Yamamoto, H., Miyagi, T., Seki, T., Tanaka, S., Hide, I. and Sakai, N.
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Journal Title
J. Pharmacol. Sci.
Volume: 122
Pages: 71-83
NAID
Related Report
Peer Reviewed
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[Journal Article] Hypoxic stress activates chaperone-mediated autophagy and modulates neuronal cell survival2011
Author(s)
Dohi, E., Tanaka, S., Seki, T, m Miyagi, T., Hide, I., Sakai, N. et al.
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Journal Title
Neurochemistry International
Volume: 60
Issue: 4
Pages: 431-442
DOI
Related Report
Peer Reviewed
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[Journal Article] Establishment of a novel fluorescence-based method to evaluate chaperone-mediate autophagy in a singlz neuron2011
Author(s)
Seki, T., Ki Y., Tanaka, S., Dohi, E., Onji, T., Yamamoto, K., Seki T, Yoshino KI, Tanaka S, Dohi E, Onji T, Yamamoto K, Hide, I., Sakai, N. et al.
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Journal Title
PLoS ONE
Volume: 7
Issue: 2
Pages: e31232-e31232
DOI
Related Report
Peer Reviewed
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