2011 Fiscal Year Final Research Report
The mechanisms of aggregation, accumulation and degradation of the genetically causative protein related to familial dementia diseases
| Project/Area Number |
21390333
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Toshihisa 大阪大学, 医学系・研究科, 講師 (10294068)
KUDO Takashi 大阪大学, 医学系・研究科, 准教授 (10273632)
MORIHARA Takashi 大阪大学, 医学系・研究科, 助教 (90403196)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 老年精神医学 |
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| Research Abstract |
Tau protein is hyperphosphorylated, ubiquitinated and accumulated in FTDP-17 brains, however mechanisms of the accumulation is still unclear. To understand the involvement of proteases in metabolisms of tau protein, some of protease inhibitors were employed in cultured cells. Pulse-chase experiments revealed proteolysis of tau protein was attenuated when treated with puromycin. And increased tau protein levels were also observed in cells treated with siRNA to puromycin-sensitive aminopeptidase(PSA) for inhibition of its expression. Those data suggest that PSA is a protease which regulates proteolysis of tau predominantly in cells. The protein metabolism of tau containing FTDP-17 mutations was also investigated employing pulse-chase experiments and attenuated proteolysis of tau was observed in the cells transfected with the mutant tau. Phosphorylation of tau at Thr231, Ser396 and Ser409 was increased in the cells transfected with V337M, R406W, and R406W mutant tau gene, respectively. These results suggest that attenuated proteolysis of FTDP-17 mutant tau might be explained by the increased phosphorylation levels resulting in resistance to proteolysis. Furthermore, in cells treated with fumagilin, an inhibitor to methionine aminopeptidase, tau protein with N-terminal methionine increased similar to puromicin-treated cells, suggesting that aminoterminal processing of tau protein is important for tau degradation.
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[Journal Article] Protein kinase C stabilizes X-linked inhibitor of apoptosis protein(XIAP) through2011
Author(s)
Kato K, Tanaka T, Sadik G, Baba M, Maruyama D, Yanagida K, Kodama T, Morihara T, Tagami S, Okochi M, Kudo T, Takeda M
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Journal Title
phosphorylation at Ser87 to suppress apoptotic cell death
Volume: 11
Pages: 90-97
Peer Reviewed
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[Journal Article] Different characteristics of cognitive impairment in elderly schizophrenia and Alzheimer' s disease in the mild cognitive impairment stage2011
Author(s)
Kazui H, Yoshida T, Takaya M, Sugiyama H, Yamamoto D, Kito Y, Wada T, Nomura K, Yasuda Y, Yamamori H, Ohi K, Fukumoto M, Iike N, Iwase M, Morihara T, Tagami S, Shimosegawa E, Hatazawa J, Ikeda Y, Uchida E, Tanaka T, Kudo T, Hashimoto R, Takeda M
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Journal Title
Dement Geriatr Cogn Dis Extra
Volume: 1(1)
Pages: 20-30
Peer Reviewed
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[Journal Article] The production ratios of AICDε51 and Aβ42 by intramembrane proteolysis ofβAPP do not always change in parallel2010
Author(s)
Mori K, Okochi M, Tagami S, Nakayama T, Yanagida K, Kodama TS, Tatsumi S, Fujii K, Tanimukai H, Hashimoto R, Morihara T, Tanaka T, Kudo T, Funamoto S, Ihara Y, Takeda M
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Journal Title
Psychogeriatrics
Volume: 10(3)
Pages: 117-123
Peer Reviewed
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[Journal Article] KIBRA genetic polymorphism influences episodic memory in Alzheimer' s disease, but does not show association with disease in a Japanese cohort2010
Author(s)
Hayashi N, Kazui H, Kamino K, Tokunaga H, Takaya M, Yokokoji M, Kimura R, Kito Y, Wada T, Nomura K, Sugiyama H, Yamamoto D, Yoshida T, Currais A, Soriano S, Hamasaki T, Yamamoto M, Yasuda Y, Hashimoto R, Tanimukai H, Tagami S, Okochi M, Tanaka T, Kudo T,
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Journal Title
Dement Geriatr Cogn Disord
Volume: 30(4)
Pages: 302-308
Peer Reviewed
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[Journal Article] The 28-amino acid form of an APLP1-derived Aβ-like peptide is a surrogate marker for Aβ42 production in the central nervous system2009
Author(s)
Yanagida K, Okochi M, Tagami S, Nakayama T, Kodama T, Nishitomi K, Jiang J, Mori K, Tatsumi S, Arai T, Ikeuchi T, Kasuga K, Tokuda T, Kondo M, Ikeda M, Deguchi K, Kazui H, Tanaka T, Morihara T, Hashimoto R, Kudo T, Steiner H, Haass C, Tsuchiya K, Akiyama
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Journal Title
EMBO Molecular Medicine
Volume: 1
Pages: 223-235
Peer Reviewed
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[Presentation] Identification of a gene which controls Abeta accumulation using APP Tg mice with mixed genetic background : Splicing variant specific-effect of Kinesin Light Chain 1(Klc1)2011
Author(s)
Morihara T, Hayashi N, Yokokoji M, Akatsu H, Saito Y, Suzuki T, Takamura A, Katayama T, Ito N, Nishitomi K, Kimura N, Kazui H, Yanagida K, Kato K, Yatsumi S, Kodama T, Tagami S, Okochi M, Tanaka T, Kudo T, Takeda M
Organizer
Alzheimer' s Association International Conference(AAIC2011)
Place of Presentation
Parris, France
Year and Date
2011-07-20
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[Presentation] Identification of a gene which controls Abeta accumulation using App Tg mice with mixed genetic background2010
Author(s)
Morihara T, Hayashi N, Yokokoji M, Fukusyo E, Tanimukai H, Tagami S, Okochi M, Tanaka T, Kudo T, Takeda M
Organizer
The 13^<th> International Conference on Alzheimer Disease and related disorders
Place of Presentation
Hawaii, USA
Year and Date
2010-07-14
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[Presentation] PIB-PET images, compared with MR, FDG-PET, and IMP-SPECT images, of a patient with Alzheimer' s disease with presenilin-1 mutation(Met233Leu) showing a new phenotype2010
Author(s)
Takaya M, Tanaka T, Ataka S, Shimada H, Morihara T, Miki T, Kazui H, Takeda M
Organizer
The 13^<th> International Conference on Alzheimer Disease and related disorders
Place of Presentation
Hawaii, USA
Year and Date
2010-07-13
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