Involvement of protein s coded by causative genes for familial dementia and ubiquitin system in neurodegenerative mechanisms

• Project/Area Number: 19390305
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: TAKEDA Masatoshi Osaka University, 医学系研究科, 教授 (00179649)
• 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)
• Research Collaborator: GOLAM Sadik 大阪大学, 医学系研究科, 特任研究員 ; YANAGI Kentaro 大阪大学, 医学系研究科, 大学院生 ; KATO Kiyoko 大阪大学, 医学系研究科, 大学院生
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2008: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2007: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
• Keywords: 前頭側頭型認知症 / 神経変性 / タウ蛋白 / ユビキチン / プロテオソーム / 蛋白分解

Research Abstract

タウ蛋白分解機構にユビキチンシステムがどのように関与しているかに関して検討をおこなうため、培養細胞にプロテアーゼに対する各阻害剤を添加してタウ蛋白の分解過程の検討をおこなったところ、ピューロマイシンのみに分解抑制効果が認められた。さらに、FTDP-17にて報告されたV337MとR406W変異タウに関して検討をおこなったところ、分解の遅延が認められた。ピューロマイシン感受性ペプチダーゼと強制発現タウはどちらも細胞質内に局在し、変異タウ蛋白はリン酸化が亢進していたことより、変異タウの分解遅延はリン酸化亢進にともなうプロテアーゼ抵抗性によることが示唆された。

Research Products

• [Journal Article] Involvement of puromycine-sensitive aminopeptidase in proteolysis of tau protein in cultured cells, and attenuated proteolysis of FTDP-17 mutant tau (2009)
  • Author(s): Yanagi K, Tanaka T, Kato K, Sadik G, Morihara T, Kudo T, Takeda M
  • Journal Title: Psycogeriatrics (in press)
  • Peer Reviewed
• [Journal Article] Differential interaction and aggregation of 3-repeat and 4-repeat tau isoforms with 14-3-3zeta protein (2009)
  • Author(s): Sadik G, Tanaka T., Kato K, Yanagi K, Kudo T, Takeda M
  • Journal Title: Biochem Biophys Res Commun 383(1) Pages: 37-41
  • Peer Reviewed
• [Journal Article] Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein : Implications for the mechanism of tau aggregation (2009)
  • Author(s): Sadik G, Tanaka T., Kato K, Yanagi K, Morihara T, Takeda M
  • Journal Title: J Neurochem 108 Pages: 33-34
  • Peer Reviewed
• [Journal Article] Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein : implications for the mechanism of tau aggregation. (2009)
  • Author(s): Sadik G, Tanaka T, Kato K, Yamamori H, Nessa BN, Morihara T, Takeda M.
  • Journal Title: J Neurochem 108 Pages: 33-43
  • Peer Reviewed
• [Journal Article] Decrease of dynamin 2 levels in late-onset Alzheimer's disease alters Abeta metabolism (2009)
  • Author(s): Kamagata E, Kudo T, Kimura R, Tanimukai H, Morihara T, Sadik G, Kamino K, Takeda M.
  • Journal Title: Biochem Biophys Res Commun (未定)
  • Peer Reviewed
• [Journal Article] Involvement of puromycin -sensitive aminopeptidase in proteolysis of tau protein in cultured cells, and attenuated proteolysis of FTDP-17 mutant tau. (2009)
  • Author(s): Yanagi K, Tanaka T, Kato K, Sadik G, Morihara T, Takeda M.
  • Journal Title: Psycogeriatrics 9(未定)
  • Peer Reviewed
• [Journal Article] Mild Cognitive Impairment (MCI) and Subjective Cognitive Impairment (SCI) (2008)
  • Author(s): Takeda M, Morihara T, Okochi M, Sadik G, Tanaka T
  • Journal Title: Psycogeriatrics 8 Pages: 155-160
  • Peer Reviewed
• [Journal Article] Dynamin 2 gene is a novel susceptibility gene for late-onset Alzheimer disease in non-APOE-epsilon4 carriers (2008)
  • Author(s): Aidaralieva NJ, Kamino K, Kimura R, Yamamoto M, Morihara T, Kazui H, Hashimoto R, Tanaka T, Kudo T, Kida T, Okuda J, Uema T, Yamagata H, Miki T, Akatsu H, Kosaka K, Takeda M.
  • Journal Title: J Hum Genet 53 Pages: 296-302
  • Peer Reviewed
• [Journal Article] Post-marketing surveillance of donepezil hydrochloride in Japanese patients with Alzheimer's disease with behavioral and psychological symptoms of dementia (BPSD) (2008)
  • Author(s): Tanaka T., Kazui H., Tanimukai H., Morihara H., Sadik G., Kudo T., Takeda M.
  • Journal Title: Psycogeriatrics 8 Pages: 114-123
  • Peer Reviewed
• [Journal Article] Processes of β-amyloid and intracellular cytoplasmic domain generation by presenilin/γ-Secretase (2008)
  • Author(s): Tagami S., Okochi M., Fukumori A., Jingwei J., Yanagida K., Nakayama T., Morihara T., Tanaka T., Kudo T., Takeda M.
  • Journal Title: Neurodegenerative Dis. 5 Pages: 160-162
  • Peer Reviewed
• [Journal Article] Regulation of Notch signaling by dynamic changes in the precision in S3 cleavage of Notch-1 (2008)
  • Author(s): Tagami S., Okochi M., Yanagida K., Ikuta A., Fukumori A., Matsumoto N., Ishizuka-Katsura Y., Nakayama T., Ito N., Jiang J., Nishitomi K., Kamino K., Morihara T., Hashimoto R., Tanaka T., Kudo T., Chiba S., Takeda M.
  • Journal Title: Mol Cell Biol 28 Pages: 165-176
  • Peer Reviewed
• [Journal Article] The 13th congress of IPA and recent expansion of researches into psychogeriatric (2008)
  • Author(s): Tanaka T., Tomioka M., Sadik G, Takeda M.
  • Journal Title: Psycogeriatrics 8 Pages: 1-3
  • Peer Reviewed
• [Journal Article] Post-marketing surveillance of donepezil hydrochloride in Japanese patients with Alzheimer's disease with behavioral and psychological symptoms of dementia(BPSD). (2008)
  • Author(s): Tanaka T., Kazui H., Tanimukai H., Morihara H., Sadik G., Kudo T., Takeda M.
  • Journal Title: Psycogeriatrics 8 Pages: 114-123
  • Peer Reviewed
• [Journal Article] Mild Cognitive Impairment (MCI)and Subjective Cognitive Impairment (SCI) (2008)
  • Author(s): Takeda M, Morihara T, Okochi M, Sadik G, Tanaka T
  • Journal Title: Psycogeriatrics 8 Pages: 155-160
  • Peer Reviewed
• [Journal Article] Processes of beta-amyloid and intracellular cytoplasmic domain generation bypresenilin/gamma-secretase. (2008)
  • Author(s): Tagami s, Okochi M, Fukumori A, Jiang J, Yanagida K, Nakayama T, Morihara T, Tanaka T, Kudo T, Takeda M.
  • Journal Title: Neurodegener Dis 5 Pages: 160-162
  • Peer Reviewed
• [Journal Article] Association between quality of life of demented patients and professionalknowledge of care workers. (2008)
  • Author(s): Kazui H, Harada K, Eguchi YS, Tokunaga H, Endo H, Takeda M. J
  • Journal Title: Geriatr Psychiatry Neurol 21 Pages: 72-78
  • Peer Reviewed
• [Journal Article] Event-related synchronization of alpha activity in early Alzheimer's disease and mild cognitive impairment : an MEG study combining beamformer and groupcomparison. (2008)
  • Author(s): Kurimoto R, Ishii R, Canuet L, Ikezawa K, Azechi M, Iwase M, Yoshida T, Kazui H, Yoshimine T, Takeda M.
  • Journal Title: Neurosci Lett 443 Pages: 86-89
  • Peer Reviewed
• [Journal Article] Biological markers as outcome measures for Alzheimer's disease interventions-real problems and future possibilities (2007)
  • Author(s): Takeda M, Okochi M, Tagami S, Tanaka T, Kudo T.
  • Journal Title: Int Psychogeriatr 19 Pages: 391-400
  • Peer Reviewed
• [Journal Article] The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between {beta}-amyloid production and tau phosphorylation in Alzheimer disease (2007)
  • Author(s): R, Tanaka T, Kudo T, Yamagata H, Tabara Y, Miki T, Akatsu H, Kosaka K, Funakoshi E, Nishitomi K, Sakaguchi G, Kato A, Hattori H, Uema T, Takeda M.
  • Journal Title: Hum Mol Genet 16 Pages: 15-23
  • Peer Reviewed
• [Journal Article] Biological markers as outcome measures for Alzheimer's disease interventions-real problems and future possibilities. (2007)
  • Author(s): Takeda M, Okochi M, Tagami S, Tanaka T, Kudo T.
  • Journal Title: Int Psychogeriatr. 19 Pages: 391-400
  • Peer Reviewed
• [Journal Article] The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between{beta}-amyloid production and tau phosphorylation in Alzheimer disease. (2007)
  • Author(s): Kimura R, Kamino K, Yamamoto M, Nuripa A, Kida T, Kazui H, Hashimoto R Tanaka T, Kudo T, Yamagata H, Tabara Y, Miki T, Akatsu H, Kosaka K, Funakoshi E, Nishitomi K, Sakaguchi G, Kato A, Hattori H, Uema T, Takeda M
  • Journal Title: Hum Mol Genet 16 Pages: 15-23
  • Peer Reviewed
• [Journal Article] Regulation of Notch signaling by dynamic changes in the precision in S3 cleavage of Notch-1. (2007)
  • Author(s): Tagami S., Okochi M., Yanagida K., Ikuta A., Fukumori A., Matsumoto Nishizuka-Katsura Y., Nakayama T., Ito N., Jiang J., Nishitomi K., Kamino K., Morihara T., Hashimoto R., Tanaka T., Kudo T., Chiba S., Takeda M.
  • Journal Title: Mol Cell Biol 28 Pages: 165-176
  • Peer Reviewed
• [Presentation] 14-3-3 Protein is a potential candidate inducer for fibrillization of 3-repeat (2008)
  • Author(s): Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
  • Organizer: Tau Soociety for Neuroscience the 38^<th> Annual Meeting
  • Place of Presentation: Washington, U.S.A.
• [Presentation] GSK3抑制によるカスペース阻害因子XIAPの亢進機序について (2008)
  • Author(s): 加藤希世子、田中稔久、Golam Sadik, 柳健太郎、武田雅俊
  • Organizer: 第27回日本認知症学会
  • Place of Presentation: 群馬県前橋市
• [Presentation] Involvement of tau protein in neurodegeneration (2008)
  • Author(s): Tanaka T, Sadik G, Kato K, Yanagi K, Takeda M
  • Organizer: 第51回日本神経化学大会
  • Place of Presentation: 富山
• [Presentation] 14-3-3 differentially induces 3-repeat and 4-repeat tau aggregation (2008)
  • Author(s): Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
  • Organizer: 第51回日本神経化学大会
  • Place of Presentation: 富山
• [Presentation] 14-3-3 Protein Exhibits Strong Affinity for 3-repeat Tau and Increases Its Filament Formation (2008)
  • Author(s): Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
  • Organizer: The 11^<th> international conference on Alzheimer disease and related disorders
  • Place of Presentation: Chicago, U.S.A.
• [Presentation] 14-3-3 Protein Exhibits Strong Affinity for 3-repeat Tau and Increases Its Filament Formation (2008)
  • Author(s): Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
  • Organizer: The 11th international conference on Alzheimerdisease and related disorders
  • Place of Presentation: Chicago USA
• [Presentation] Drastic Impact on Abeta Accumulation in APP Tg Mice By Genetic Background. (2008)
  • Author(s): Morihara T, Yokokoji M, Hayashi N, Noshi E, Mori K, Tagami S, Kudo T, Kamino K, Taked M
  • Organizer: The 11th international conference on Alzheimerdisease and related disorders
  • Place of Presentation: Chicago USA
• [Presentation] Involvement of tau protein in neurodegeneration (2008)
  • Author(s): Tanaka T, Sadik G, Kato K, Yanagi K, Takeda M
  • Organizer: 第51回神経化学大会
  • Place of Presentation: 富山
• [Presentation] 14-3-3 differentially induces 3-repeat and 4-repeat tau aggregation (2008)
  • Author(s): Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
  • Organizer: 第51回神経化学大会
  • Place of Presentation: 富山
• [Presentation] Risk Genes for Dementia (2008)
  • Author(s): 森原剛史, 紙野晃人, 数井裕光, 林紀行, 横小路美貴子, 工藤喬, 武田雅俊
  • Organizer: 第51回神経化学大会
  • Place of Presentation: 富山
• [Presentation] アルツハイマー病モデルマウス(APP Tg)のアミロイド病理は背景遺伝子で大きく変わる (2008)
  • Author(s): 横小路美貴子, 森原剛史, 林紀行田上真次, 武田雅俊
  • Organizer: 第51回神経化学大会
  • Place of Presentation: 富山
• [Presentation] GSK3抑制によるカスベース阻害因子XIAPの亢進機序について (2008)
  • Author(s): 加藤希世子, 田中稔久, Golam Sadik, 柳健太郎, 武田雅俊
  • Organizer: 第27回日本認知症学会学術集会
  • Place of Presentation: 前橋
• [Presentation] APP TgマウスのAβ蓄積量はマウス背景遺伝子の違いで大きく変わる (2008)
  • Author(s): 森原剛史, 横小路美貴子, 林紀行, 田上真次, 工藤喬, 熨斗英理子, 伊藤尚弘, 西富晃平, 武田雅俊
  • Organizer: 第27回日本認知症学会学術集会
  • Place of Presentation: 前橋
• [Presentation] 14-3-3 Protein Exhibits Strong Affinity for 3-repeat Tau and Increases Its Filament Formation (2008)
  • Author(s): Sadik G, Tanaka T, Kato K, Yanagi K, Takeda M
  • Organizer: Soociety for Neuroscience the 38th Annual Meeting
  • Place of Presentation: Washington, U. S. A.
• [Presentation] Genetic approaches in Dmentia Study (2007)
  • Author(s): Tanaka T, Kamino K, Morihara T, Sadik G, Kimura R, Kudo T, Takeda M.
  • Organizer: Japan-Taiwan Dementia Symposium
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2007-10-13
• [Presentation] FTDP-17 mutations of tau affect the interaction between tau and 14-3-3 (2007)
  • Author(s): Sadik G, Tanaka T, Kato K, Takeda M
  • Organizer: Soociety for Neuroscience the 37^<th> Annual Meeting
  • Place of Presentation: San Diego, U.S.A.
• [Presentation] Symposium S34, Prevention, early diagnosis and treatment of dementia (2007)
  • Author(s): Tanaka T, Kazui H, Morihara T, Kamino K, Okochi M, Tagami S, Kudo T, Takeda M.
  • Organizer: The 13^<th> Congress of the International Psychogeriatrics Association
  • Place of Presentation: Osaka, Japan
• [Presentation] Increased expression of Toll like receptor 3 in Alzheimer disease brain (2007)
  • Author(s): Tanaka T, Nessa BN, Sadik G, Kato K, Takeda M.
  • Organizer: The 13^<th> Congress of the International Psychogeriatrics Association
  • Place of Presentation: Osaka, Japan
• [Presentation] Toll like receptor 3 mediated pathogenesis in Alzheimer's disease (2007)
  • Author(s): Nessa BN, Tanaka T, Kamino K, Sadik G, Ansar AB, Kudo T, Takeda M.
  • Organizer: The 13^<th> Congress of the International Psychogeriatrics Association
  • Place of Presentation: Osaka, Japan
• [Presentation] Phosphorylation of tau with or without FTDP-17 mutations similarly affects the interaction with 14-3-3 protein (2007)
  • Author(s): Sadik G, Tanaka T, Kato K, Takeda M
  • Organizer: The 13^<th> Congress of the International Psychogeriatrics Association
  • Place of Presentation: Osaka, Japan
• [Presentation] Neuroprotective effects of lithium (2007)
  • Author(s): Kato K, Tanaka T, Sadik G, Takeda M.
  • Organizer: The 13^<th> Congress of the International Psychogeriatrics Association
  • Place of Presentation: Osaka, Japan
• [Presentation] Degradation of tau protein in cultured cells (2007)
  • Author(s): Yanagi K, Tanaka T, Sadik G, Kato K, Takeda M.
  • Organizer: The 13^<th> Congress of the International Psychogeriatrics Association
  • Place of Presentation: Osaka, Japan
• [Presentation] γSecretase inhibitors DAPT and L-685,458 perturb Wnt signaling (2007)
  • Author(s): Nakayama T, Okochi M, Tagami S, Yanagida K, Nishitomi K, Oguri T, Jiang J, Mori K, Morihara T, Hashimoto R, Tanaka T, Kudo T, Takeda M.
  • Organizer: The 13^<th> Congress of the International Psychogeriatrics Association
  • Place of Presentation: Osaka, Japan.
• [Presentation] FTDP-17 mutations of tau affect the interaction between tau and 14-3-3 (2007)
  • Author(s): Sadik G, Tanaka T, Kato K Takeda M
  • Organizer: Soociety for Neuroscience, the 37th Annual Meeting
  • Place of Presentation: San Diego, U.S.A.
• [Presentation] Prevention, early diagnosis and treatment of dementia. (2007)
  • Author(s): Tanaka T, Kazui H, Morihara T, Kamino K, Okochi M, Tagami S, Kudo T, Takeda M.
  • Organizer: The 13th Congress of the International Psychogeriatrics Association
  • Place of Presentation: Osaka, Japan.
• [Book] タウオパチー、KEY WORD 精神 第4版 (2007)
  • Author(s): 田中稔久、武田雅俊
  • Publisher: 先端医学社(東京)