Elucidation of the involvement of chaperone-mediated autophagy in the pathogenesis of neurodegenerative and psychiatric disorders
| Project/Area Number |
25430065
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Kumamoto University |
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Principal Investigator |
Seki Takahiro 熊本大学, 大学院生命科学研究部, 准教授 (50335650)
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| Project Period (FY) |
2013-04-01 – 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 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | シャペロン介在性オートファジー / ミクロオートファジー / パーキンソン病 / 神経細胞 / リソソームタンパク質分解系 / 神経変性疾患 |
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| Outline of Final Research Achievements |
In the present study, we attempted to establish a novel method to monitor chaperone-mediated autophagy (CMA) and microautophagy (mA) acitivities, separately. siRNA-mediated knockdown of CMA- and mA-related proteins enabled us to assess CMA and mA activities, separately, in cells expressing GAPDH-HT, a reporter protein of CMA/mA activity. Using this method, we revealed that the CMA/mA activity is significantly decreased in drug-induced cell model of Pakinson's disease. Moreover, a chemical that activates CMA prominently inhibited cell death in this model. These findings strongly suggest that distrubance of CMA/mA activity would render the pathogenesis of Parkinson's disease.
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Report
(4 results)
Research Products
(68 results)
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[Journal Article] A knockin mouse model of spinocerebellar ataxia type 3 exhibits prominent aggregate pathology and aberrant splicing of the disease gene transcript2015
Author(s)
Ramani B, Harris GM, Huang R, Seki T, Murphy GG, Costa Mdo C, Fischer S, Saunders TL, Xia G, McEachin RC, Paulson HL
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Journal Title
Human Molecular Genetics
Volume: 24
Issue: 5
Pages: 1211-1224
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification and characterization of PKCγ, a kinase associated with SCA14, as an amyloidogenic protein.2015
Author(s)
Takahashi H, Adachi N, Shirafuji T, Danno S, Ueyama T, Vendruscolo M, Shuvaev AN, Sugimoto T, Seki T, Hamada D, Irie K, Hirai H, Sakai N, *Saito N.
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Journal Title
Hum Mol Genet.
Volume: 24
Issue: 2
Pages: 525-539
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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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] 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] 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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