2012 Fiscal Year Final Research Report
Elucidation of the involvement ofchaperone-mediated autophagy to the pathogenesis of neurodegenerative diseases using a novel method to monitor its activity
| Project/Area Number |
23700450
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Hiroshima University |
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Principal Investigator |
SEKI Takahiro 広島大学, 大学院・医歯薬保健学研究院, 助教 (50335650)
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| Project Period (FY) |
2011 – 2012
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| Keywords | シャペロン介在性オートファジー / 脊髄小脳失調症 |
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| Research Abstract |
Chaperone-mediated autophagy (CMA) isone of the proteolytic pathways. Since there is no simple method to monitor CMA activity, the roles of CMA in physiological functions and pathogenesis of diseases have remained unknown. In the present study, I have established a novel method to monitor CMA activity in a single cell level. To utilize this method, I revealed that mutant γPKC which causes spinocerebellar ataxia type 14(SCA14) impairs CMA activity in primary cultured neural cells. In addition, I elucidated that the amounts of proteins related to CMA are altered in the brain of SCA3, another type of SCA, model mice. These findings suggest that CMA might be related to the pathogenesis of two different types of SCAs.
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Research Products
(37 results)
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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, M., Miyagi, T., Seki, T., Tanaka, T., Hide, I. and Sakai, N
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Journal Title
J. Pharmacol. Sci
Pages: in press
Peer Reviewed
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[Journal Article] Long-term exposure of RN46A cells expressing serotonin transporter (SERT) to a cAMP analog up-regulates SERT activity and is accompanied by neural differentiation of the cells2013
Author(s)
Yamamoto, H., Tanaka, S., Tanaka, A., Hide, I., Seki, T. and Sakai, N
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Journal Title
J. Pharmacol. Sci.
Volume: 121
Pages: 25-38
Peer Reviewed
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[Journal Article] Inhibitory effects of levetiracetam on the high-voltage-activated L-type Ca~2+channels in hippocampal CA3 neurons of spontaneously epileptic rat (SER).2012
Author(s)
Yan, H.D., Ishihara, K., Seki, T., Hanaya, R., Kurisu, K., Arita, K., Serikawa, T. and Sasa, M.
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Journal Title
Brain Res. Bull.
Volume: 90
Pages: 142-148
Peer Reviewed
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[Journal Article] Establishment of a novel fluorescence-based method to evaluate chaperone-mediated autophagy in a single neuron.2012
Author(s)
Seki, T., Yoshino, K.I, Tanaka, S., Dohi, E., Onji, T., Yamamoto, K., Hide, I., Paulson, H.L., Saito, N. and Sakai, N.
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Journal Title
PLoS One
Volume: 7
Pages: e31232
Peer Reviewed
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[Journal Article] Hypoxic stress activates chaperone-mediated autophagy and modulates neuronal cell survival.2012
Author(s)
Dohi, E., Tanaka, S., Seki, T., Miyagi, T., Hide, I., Takahashi, T., Matsumoto, M. and Sakai N.
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Journal Title
Neurochem. Int.
Volume: 60
Pages: 431-442
Peer Reviewed
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[Journal Article] Mutant PKCγin spinocerebellar ataxia type 14 disrupts synapse elimination and long-term depression in Purkinje cells in vivo2011
Author(s)
Shuvaev, A.N., Horiuchi, H., Seki, T., Goenawan, H., Irie, T., Iizuka, A., Sakai, N. and Hirai, H.
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Journal Title
J. Neurosci.
Volume: 31
Pages: 14324-14334
Peer Reviewed
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[Journal Article] Elucidation of the molecular mechanism and exploration of novel therapeutics for spinocerebellar ataxia caused by mutant protein kinase Cγ.2011
Author(s)
Seki, T., Adachi, N., Abe-Seki, N., Shimahara, T., Takahashi, H., Yamamoto, K., Saito, N. and Sakai, N.
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Journal Title
J. Pharmacol. Sci.
Volume: 116
Pages: 239-247
Peer Reviewed
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