2012 Fiscal Year Final Research Report
Development of therapeutic strategy for intractable neuropsychiatric disease using chemical chaperones
| Project/Area Number |
22390049
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Hiroshima University |
|---|
Principal Investigator |
SAKAI Norio 広島大学, 大学院・医歯薬保健学研究院, 教授 (70263407)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
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)
SEKI Takahiro 広島大学, 大学院・医歯薬保健学研究院, 助教 (50335650)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Keywords | ケミカルシャペロン シャペロン介在性オートファジー / セロトニントランスポーター / γPKC |
|---|
| Research Abstract |
(1) Congo red inhibited the aggregate formation of mutant ・PKC, which caused spinocerebellar ataxia type 14 (SCA14), thereby, the cytotoxicity of SCA14 mutant ・PKC was reduced.
(2) It is believed that 30 % of proteins are degraded by the chaperone-mediated autophagy (CMA). We developed the fluorescent-based probe, HaloTag-fused GAPDH, which can evaluate the cellular activity of CMA in single cell level. Using this probe, we demonstrated that CMA is inhibited in cells expressing SCA14 mutant ・PKC.
(3) We revealed that 4-phenylbutylate (4-PBA), a chemical chaperone, increased the serotonin uptake activity of serotonin transporter (SERT) probably by accelerating SERT membrane trafficking.
|
-
[Journal Article] a membrane-targeted deubiquitinating enzyme, is activated by ubiquitination and regulatesmembrane dynamics, cell motility and endocytosis2013
Author(s)
Seki, T., Gong, J., Williams, A. J., Sakai, N., Todi, S. V. and Paulson, H. L. JosD1
-
Journal Title
Peer Reviewed
-
[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. and Sakai, N
-
Journal Title
Peer Reviewed
-
-
[Journal Article] Hypoxic stress activates chaperone-mediated autophagy and modulates neuronal cell survival2012
Author(s)
Dohi, E., Tanaka, S., Seki, T., Miyagi, T., Hide, I., Takahashi, T., Matsumoto, M. and Sakai, N
-
Journal Title
Neurochem. Int
Volume: 60
Pages: 431-442
Peer Reviewed
-
[Journal Article] Establishment of a novel fluorescence-based method to evaluate chaperone-mediated autophagy in a single neuron2012
Author(s)
Seki, T., Yoshino, K., Tanaka, S., Dohi, E., Onji, T., Yamamoto, K., Hide, I., Paulson, H.L., Saito, N. and Sakai. N
-
Journal Title
PLoS ONE
Volume: 7
Pages: e31232
Peer Reviewed
-
-
[Journal Article] Mutant PKC・in 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., Hanna, G., Irie, T., Iizuka, A., Sakai, N. and Hirai, H
-
Journal Title
J. Neuroscience
Volume: 31
Pages: 14324-14334
Peer Reviewed
-
[Journal Article] Elucidation of the molecular mechanism and exploration of novel therapeutics for spinocerebellar ataxia caused by mutant protein kinase Cγ2011
Author(s)
Seki, T., Adachi, Abe-Seki, N., Shimahara, T., Takahashi, H., Yamamoto, K., Saito, N. and Sakai, N
-
Journal Title
J. Pharmacol. Sci
Volume: 116
Pages: 239-247
Peer Reviewed
-
[Journal Article] Direct binding of RalA to PKCηand its crucial role in morphological change during keratinocytes differentiation2011
Author(s)
Shirai, Y. Morioka, S., Sakuma, M., Yoshino, K., Otsuji, C., Sakai, N., Kashiwagi, K., Chida. K., Shirakawa, R., Horiuchi, H., Nishigori, C., Ueyama, T. and Saito, N
-
Journal Title
Mol. Biol. Cell
Volume: 22
Pages: 1340-1352
Peer Reviewed
-
[Journal Article] Extracellular ATP differentially modulates Toll-like receptor 4-mediated cell survival and death of microglia2011
Author(s)
Harada, K., Hide, I., Seki, T., Tanaka, S., Nakata, Y. and Sakai, N
-
Journal Title
J. Neurochem
Volume: 116
Pages: 1138-1147
Peer Reviewed
-
[Journal Article] A critical role for conventional protein kinase C in morphological changes of rodent mast cells2011
Author(s)
Yanase, Y., Hide, I., Mihara, S., Shirai, Y., Saito, N., Nakata, Y., Hide, M. and Sakai, N
-
Journal Title
Immunol. Cell Biol
Volume: 89
Pages: 149-159
Peer Reviewed
-
[Journal Article] Congo red, an amyloid-inhibiting compound, alleviates various cellular dysfunction triggered by mutant protein kinase Cγthat causes spinocerebellar ataxia type 14 (SCA14) by inhibiting oligomerization and aggregation2010
Author(s)
Seki, T., Takahashi, H., Yamamoto, K., Ogawa, K., Onji, T., Adachi, N., Tanaka, S., Hide, I., Saito, N. and Sakai, N
-
Journal Title
J. Pharmacol. Sci
Volume: 114
Pages: 206-216
Peer Reviewed
-
[Journal Article] The effect of trehalose on the properties of mutant γPKC, which causes spinocerebellar ataxia type 14 (SCA14), in neuronal cell lines and cultured Purkinje cells2010
Author(s)
Seki, T., Abe-Seki, N., Kikawada, T., Takahashi, H., Yamamoto, K., Adachi, N., Tanaka, S., Hide, I., Saito, N. and Sakai, N
-
Journal Title
J Biol. Chem
Volume: 285
Pages: 33252-33264
Peer Reviewed
-
[Journal Article] Mutant protein kinase C gamma that causes spinocerebellar ataxia type 14 (SCA14) is selectively degraded by autophagy2010
Author(s)
Yamamoto, K., Seki, T., Adachi, N., Takahashi, T. Tanaka, S., Hide, I., Saito, N. and Sakai, N
-
Journal Title
Genes to Cells
Volume: 15
Pages: 425-437
Peer Reviewed
-
[Journal Article] Stimulatory effects of the soy phytoestrogen genistein on noradrenalin transporter and serotonin transporter activity2010
Author(s)
Toyohira, Y., Ueno, S., Tsutsui, M., Itho, H., Sakai, N., Saito, N., Takahashi, K. and Yanagihara, N
-
Journal Title
Mol. Nurt. and Food Res
Volume: 54
Pages: 516-24
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
