2009 Fiscal Year Final Research Report
Identification of therapeutic targets by genetic studies of neurodegeneration signal
| Project/Area Number |
17025010
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MIURA Masayuki The University of Tokyo, 大学院・薬学系研究科, 教授 (50202338)
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| Project Period (FY) |
2005 – 2009
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| Keywords | モデル生物 / ショウジョウバエ / 細胞死 / 神経変性 / プロテアソーム |
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| Research Abstract |
The ubiquitin-proteasome system, which contributes to protein quality control by degrading unfolded or misfolded proteins, is closely related to the etiology of neurodegenerative disorders. The 26S proteasome is composed of one, proteolytically active, core particle (alias 20S proteasome) and one or two 19S regulatory particles subdivided into lid and base subcomplexes. In a genetic gain-of-function screen, we identified one of the lid subunits as a suppressor of expanded polyglutamine-induced neurodegenerative phenotypes in a Drosophila disease model. Our results suggest that an age-related reduction in 26S proteasome activity is the key factor of the increased risk for late-onset of neurodegeneration, and implicate that keeping the amount of the 26S proteasome by providing an overexpressed lid subunit will provide a way to delay the onset of neurodegeneration in vivo.
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[Journal Article] Caspase-9 activation revealed by Semaphorin 7A cleavage is independent of apoptosis in the aged olfactory bulb.2009
Author(s)
Ohsawa, S., Hamada, S., Asou, H., Kuida, K., Uchiyama, Y., Yoshida, H., Miura, M.
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Journal Title
J. Neurosci. 29
Pages: 11385-11392
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[Journal Article] Genetic evidence linking age-dependent attenuation of the 26S proteasome with aging process.2009
Author(s)
Tonoki, A., Kuranaga, E., Tomioka, T., Hamazaki, J., Murata, S., Tanaka, K., Miura, M.
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Journal Title
Mol Cell Biol. 29
Pages: 1095-1106
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[Journal Article] Drosophila IKK-related kinase regulates nonapoptotic function of caspases via degradation of IAPs.2006
Author(s)
Kuranaga, E., Kanuka, H., Tonoki, A., Takemoto, K., Tomioka, T., Kobayashi, M., Hayashi, S., Miura, M.
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Journal Title
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[Journal Article] Gain-of-function screen identifies a role of the Sec61αtranslocon in Drosophila postmitotic neurotoxicity.2005
Author(s)
Kanuka, H., Hiratou, T., Igaki, T., Kanda, H., Kuranaga, E., Sawamoto, K., Aigaki, T., Okano, H., Miura, M.
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Journal Title
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[Presentation] Involvement of the 26S proteasome in the age-related neurodegenerative diseases.2008
Author(s)
Tonoki, A., Kuranaga, E., Tomioka, T., Hamazaki, J., Murata, S., Tanaka, K., Miura, M.
Organizer
BMB 2008 Symposium
Place of Presentation
Kobe, Japan
Year and Date
20081209-20081212
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