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

2008 Fiscal Year Final Research Report

• 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
• 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] 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] 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
• [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.
  • Year and Date: 20081115-19
• [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
  • Year and Date: 20081010-12
• [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
  • Year and Date: 20080911-13
• [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
  • Year and Date: 20080911-13
• [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.
  • Year and Date: 20080726-31
• [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.
  • Year and Date: 20071103-07
• [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
  • Year and Date: 20071014-18
• [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
  • Year and Date: 20071014-18
• [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
  • Year and Date: 20071014-18
• [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
  • Year and Date: 20071014-18
• [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
  • Year and Date: 20071014-18
• [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
  • Year and Date: 20071014-18
• [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.
  • Year and Date: 20071014-18
• [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
• [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
  • Total Pages: 188-189
  • Publisher: 先端医学社(東京)