Selective protein degradation with the aim of developing therapies for neurodegenarative diseases
| Project/Area Number |
26293207
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
岡田 和将 産業医科大学, 医学部, 講師 (30341499)
岩中 行己男 産業医科大学, 医学部, 助教 (60590461)
橋本 智代 産業医科大学, 医学部, 助教 (70425685)
黄 哲 産業医科大学, 医学部, 助教 (30745112)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | 神経変性疾患 / オートファジー / 分子シャペロン / ユビキチン・プロテアソーム系 / TFEB / HIKESHI / ポリグルタミン病 / 球脊髄性筋萎縮症 / 筋萎縮性側索硬化症 / ユビキチンｰプロテアソーム系 |
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| Outline of Final Research Achievements |
The transcription factor EB (TFEB) has been reported to regulate autophagy by upregulating genes that belong to the coordinated lysosomal expression and regulation (CLEAR) network, thereby controlling lysosomal biogenesis. Hikeshi is essential for the entry of the Hsc70/Hsp70 (Hsp70s) to the nucleus under stress condition. We examined the effects of the overexpression of TFEB and Hikeshi in cultured cell models of neurodegenerative diseases. Neuronal cells were transfected with plasmids encoding mutant androgen receptor, huntingtin, ataxin-1, ataxin-3, Hikeshi and TFEB. The overexpression of TFEB and Hikeshi decreased the expression of each causative protein in the neuronal cell models. Hikeshi could interact with TFEB and enhance the degradation of the disease-causative proteins. On the other hand, reduction of TFEB and Hikeshi slows the turnover of mutant proteins. These findings demonstrated that TFEB and Hikeshi influence the degradation of the disease-causative proteins.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] BIIB021, a synthetic Hsp90 inhibitor, induces mutant ataxin-1 degeneration through the activation of heat shock factor 1.2016
Author(s)
Ding Y, Adachi H, Katsuno M, Sahashi K, Kondo N, Iida M, Tohnai G, Nakatsuji H, Sobue G
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Journal Title
Neuroscience
Volume: S0306-4522
Pages: 30051-30053
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Impaired muscle uptake of creatine in spinal and bulbar muscular atrophy.2016
Author(s)
Hijikata Y., Katsuno M., Suzuki K., Hashizume A., Araki A., Yamada S., Inagaki T., Iida M., Noda S., Nakanishi H., Banno H., Mano T., Hirakawa A., Adachi H., Watanabe H., Yamamoto M., Sobue G.
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Journal Title
Ann Clin Transl Neurol
Volume: 3
Issue: 7
Pages: 537-546
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] FUS/TLS acts as an aggregation-dependent modifier of polyglutamine disease model mice.2016
Author(s)
Kino Y, Washizu C, Kurosawa M, Yamada M, Doi H, Takumi T, Adachi H, Katsuno M, Sobue G, Hicks GG, Hattori N, Shimogori T, Nukina N.
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Journal Title
Sci Rep.
Volume: 6
Issue: 1
Pages: 35236-35236
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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