Study on involvement of of tau-binding factors in neurodegeneration

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18591286
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: TANAKA Toshihisa Osaka University, Graduate School of Medicine, Associate Professor (10294068)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Masatoshi Osaka Univetsty, Graduate School of Medicine, Professor (00179649) ; MORIHARA Takashi Osaka Univetsty, Graduate School of Medicine, Assistant Professor (90403196)
• Project Period (FY): 2006 – 2007
• Keywords: Tau urotein / 14-3-3 protein / Phosphorylation / Protein kinase

Research Abstract

Neurofibrillary tangles are neuropathological hallmarks of Alzheimer disease (AD) and other tauopathies including frontotemporal dementia (FTD) and corticobasal degeneration, and abnormally hyperphosphorylated tau protein is the major protein component of NFT. After finding of tau gene on chromosome 17 as a causative gene for familial FTD (FTDP-17), tau is thought to be essentially important for understanding of neurodegenerative processes in dementia. In brain of tauopathies tau is hyperphosphorylated and ubiquitinated, and self-assembles and forms filaments or aggregates, however the mechanisms of the involvement of tau in neurodegeneration are unclear.
To understand the mechanisms of self-assembly of tau, we investigated the effects of phosphorylation of tau on the process self-assembly induced by 14-3-3. Phosphorylation of tau by protein kinase A (PKA) or protein kinase B (PKB), not glycogen synthase kinase-3, enhanced the binding of tau with 14-3-3, however PKA- or PKB-phosphorylation abolished the self-assembly of tau protein. And we investigated the effects of FTDP-17 mutations of tau on the process self-assembly induced by 14-3-3. The mutant tau (P301L, V337M and R406W) had higher affinity with 14-3-3 than wild type tau, and P301L tau induced the highest self-assembly level than others in the presence of 14-3-3. Our results suggest that phosphorylation and mutations of tau might play an important role in self-assembly of tau.

Research Products

• [Journal Article] Biological markes 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
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The DYRK1A gene, encded in chromosome 21 Down syhdrome 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, 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
  • Description: 「研究成果報告書概要(和文)」より
  • 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 N., Ishizuk a-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
  • Description: 「研究成果報告書概要(和文)」より
  • 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
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between {beta}-amyloid production and tau phosphorylation hi 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, Mild 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
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 「研究成果報告書概要(欧文)」より (2007)
  • 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
  • Journal Title: Mol Cell Biol 28 Pages: 165-176
• [Journal Article] Neurobiological studies of dementia-biological markers and neuroprotective strategies for Alzheimer disease. (2006)
  • Author(s): Tanaka T, Isoe-Wada K, Yamamori H, Kato K, Nessa BN, Sadik GM, Takeda M.
  • Journal Title: Acta Neurol Taiwan. 15 Pages: 68-71
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Presenilin-dependent gamma-secretase on plasma membrane and endosomes isfunctionally distinct. (2006)
  • Author(s): Fukumori A, Okochi M, Tagami S, Jiang J, Itoh N, Nakayama T, Yanagida K, Ishzuka-Katsura Y, Morihara T, Kamino K, Tanaka T, Kudo T, Tanii H, Ikuta A, Haass C, Takeda M.
  • Journal Title: Biochemistry 45 Pages: 4907-4914
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Neurobiological studies of dementia-biological markers and neuroprotective strategies for Alzheimer disease (2006)
  • Author(s): Tanaka, T, Isoe-Wada, K, Yamamori, H, Kato, K, Massa, BN, Sadik, GM, Takeda, M
  • Journal Title: Acta Neurol Taiwan 15 Pages: 68-71
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Presenilindependent gamma-secretase on plasma membrane and endosomes is functionally distinct (2006)
  • Author(s): Fukumori, A, Okochi, M, Tagami, S, Jiang, J, Itoh, N, Nakayama, T, Yanagida, K, Ishizuka-Katsura, Y, Morihara T, Kamino K, Tanaka T. Kudo T, Tanii H, Ikuta A, Haass C, Takeda M
  • Journal Title: Biochemistry 45 Pages: 4907-4914
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Regulation of Notch signaling by dynamic changes in the precision in S3 cleavage of Notch-1 (2006)
  • Author(s): Morihara, T., Hashimoto, R., Tanaka, T., Kudo, T., Chiba, S., Takeda, M
  • Journal Title: Biological markers for diagnosis of MCI and neurod Pages: 101-107
  • Description: 「研究成果報告書概要(欧文)」より
• [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.
  • Year and Date: 20071103-07
  • Description: 「研究成果報告書概要(和文)」より
• [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: Convention Center in San Diego, U.S.A
  • Year and Date: 20071103-07
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] "Biological markers for diagnosis of MCI and neurodegenerative dementia", Functional and Moleculart Imaging of Stroke and Dementia (2006)
  • Author(s): Takeda M, Kudo T, Tanaka T, Kamino K, Okochi M, Tagami S
  • Total Pages: 101-107,総250
  • Publisher: Elsevier
  • Description: 「研究成果報告書概要(和文)」より