Study on interaction between apoptosis inhibitory protein and tau protein, and its implication on neurodegeneration

• Project/Area Number: 16591136
• 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, Graguate School of Medicine, Assistant Professor, 医学系研究科, 講師 (10294068)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Masatoshi Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00179649) ; KUDO Takashi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (10273632)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
• Keywords: Alzheimer disease / Tau Protein / Apoptosis

Research Abstract

Neurofibrillary tangles (NFTs) are neuropathological hallmarks of Alzheimer disease (AD) and abnormally hyperphosphorylated tau is the major protein component of NFTs. According to our previous studies on the regulation of phosphorylation of tau protein, an involvement of intrinsic anti-apoptotic factor in neurodegenerative process in AD, is speculated. Therefore XIAP (X chromosome-linked inhibitor of apoptosis), one of intrinsic anti-apoptotic proteins, was investigated in this study. First, transfected XIAP protected COS cells from death and increased phosphorylation of tau protein in cells treated with 1 μM of wortmannin, an inhibitor to phosphatidylinositol 3-kinase. Second, the binding of XIAP with N-terminal tau sequence was observed only when the first methionine was deleted. These results suggest that XIAP might be involved in neurodegenerative process of AD or tauopathy, that is slowly progressive.

Research Products

• [Journal Article] Toll like Receptor 3 mediated hyperphosphorylation of tau in human SH-SY5Y neuroblastoma cells. (2006)
  • Author(s): Begum NN, Tanaka T., Kamino K, Golam MS.Ashik BA, Kimura R, Kudo K, Takeda M
  • Journal Title: Psychiatry Clinical Neurosciences 60 Suppl. 1
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Toll-like receptor 3 mediated hyperphosphorylation of tau in human SH-SY5Y neuroblastoma cells. (2006)
  • Author(s): Nessa BN, Tanaka T, Kamino K, Sadik G, Ansar AB, Kimura R, Tanii H, Okochi M, Morihara T, Tagami S, Kudo T, Takeda M.
  • Journal Title: Psychiatry Clin Neurosci. 60 (Suppl 1)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Toll like Receptor 3 mediated hyperphosphorylation of tau in human SH-SY5Y neuroblastoma cells. (2006)
  • Author(s): Begum NN, Tanaka T., Kamino K, Golam MS.Ashik BA, Kimura, R, Kudo K, Takeda M
  • Journal Title: Psychiatry Clinical Neurosciences In press
• [Journal Article] Multiple pathogenesis of frontotemporal dementia. (2005)
  • Author(s): Tanaka, T
  • Journal Title: Psychogeriatrics 5 Pages: 15-17
  • NAID: 10018089935
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alpha-synuclein-positive structures induced in leupeptin-infused rats (2005)
  • Author(s): Nakajima T, Takauchi S, Ohara K, Kokai M, Nishii R, Maeda S, Takanaga A, Tanaka T, Takeda M, Seki M, Morita Y.
  • Journal Title: Brain Research 1040 Pages: 73-80
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] タウ蛋白修飾とアポトーシス阻害因子に関連するアルツハイマー病診断法と治療法の開発 (2005)
  • Author(s): 田中稔久, 山森英長, Begum Nurun Nessa, Md.Golam Sadik, エ藤喬, 紙野晃人, 大河内正康, 田上真次, 福森亮雄, 金山大祐, 姜経緯, 木村亮, 武田雅俊
  • Journal Title: 精神薬療研究年報 37 Pages: 69-74
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 家族性FTDの遺伝子変異 (2005)
  • Author(s): 田中稔久, 武田雅俊
  • Journal Title: 老年精神医学雑誌 16 Pages: 1033-1040
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 近未来に向けて解決すべき治療・予防戦略 タウタンパクの制御を通じたアプローチ (2005)
  • Author(s): 田中稔久, 武田雅俊
  • Journal Title: 老年精神医学雑誌 16.増刊号III Pages: 116-125
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alpha-synuclein-positive structures induced in leupeptin-infused rats. (2005)
  • Author(s): Nakajima T, Takauchi S, Ohara K, Kokai M, Nishii R, Maeda S, Takanaga A, Tanaka T, Takeda M, Seki M, Morita Y.
  • Journal Title: Brain Res. 1040 Pages: 73-80
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] タウ蛋白修飾とアポトーシス阻害因子に関連するアルツハイマー病診断法と治療法の開発 (2005)
  • Author(s): 田中稔久, 山森英長, Begum Nurun Nessa, Md.Golam Sadik, 工藤喬, 紙野晃人, 大河内正康, 田上真次, 福森亮雄, 金山大祐, 姜経緯, 木村亮, 武田雅俊
  • Journal Title: 精神薬療研究年報 37 Pages: 69-74
• [Journal Article] 近未来に向けて解決すべき治療・予防戦略 タウタンパクの制御を通じたアプローチ (2005)
  • Author(s): 田中稔久, 武田雅俊
  • Journal Title: 老年精神医学雑誌 16・増刊号III Pages: 116-125
• [Journal Article] Activated protein kinases and phosphorylated tau protein in Alzheimer disease. (2004)
  • Author(s): Tanaka T., Yamamori H., Wada-Isoe K., Tsujio I., Takeda M.
  • Journal Title: Molecular Neurobiology of Alzheimer Disease and Related Disorders (ed.by Takeda M., Tanaka T., Cacabelos R.)(Karger, Basel, Switzerland) Pages: 225-235
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Amyloid-β down-regulates XIAP expression in human SH-SY5Y neuroblastoma cells (2004)
  • Author(s): Yamamori H, et al.
  • Journal Title: Neuro Report 15(5);,2004 15・5 Pages: 851-854
• [Journal Article] タウ蛋白誘導性アポトーシスによる神経変性に対する抑制剤開発研究 (2004)
  • Author(s): 田中稔久, 山森英長, ほか
  • Journal Title: 精神薬療研究年報 36 Pages: 57-65
• [Book] Activated protein kinases and phosphorylated tau protein in Alzheimer disease. "Molecular Neurobiology of Alzheimer Disease and Related Disorders"(Editoed. by Takeda M., Tanaka T., Cacabelos R.) (2004)
  • Author(s): Tnaka T., Yamamori H., Wada-Isoe K., et al.
  • Publisher: Published by Karger co., (Basel, Switzerland)
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Activated protein kinases and phosphorylated tau protein in Alzheimer disease. "Molecular Neurobiology of Alzheimer Disease and Related Disorders"(Edited.by Takeda M., Tanaka T., Cacabelos R.) (2004)
  • Author(s): Tanaka T., Yamamori H., Wada-Isoe K., et al.
  • Publisher: Published by Karger co., (Basel, Switzerland)