Common coupling protein of amyotrophic lateral sclerosis and spinocerebellar degeneration

• Project/Area Number: 23591279
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Yokohama City University
• Principal Investigator: KOYANO Shigeru 横浜市立大学, 医学部, 准教授 (50315818)
• Co-Investigator(Kenkyū-buntansha): KUROIWA Yoshiyuki 帝京大学, 医学部, 客員教授 (40135249)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2013: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2012: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 筋萎縮性側索硬化症 / 脊髄小脳変性症 / TDP-43 / ATXN / 脳神経疾患 / ポリグルタミン病

Research Abstract

The aim of this study is clarify the common coupling protein of amyotrophic lateral sclerosis and spinocerebellar degeneration. The ATXN protein and TDP-43 protein may be combined each other. We prove this histopathologically.
(1) We measured the number of the CAG repeat in the patient of amyotrophic lateral sclerosis, but it was in the normal range. (2) Pathological intracellular inclusions in ALS were not found by immunostaining of an anti-ATXN protein antibody. Only an ataxin-2 expressed in the intracytoplasmic inclusion body of the dentate gyrus of the part in case of ALS with dementia. (3) Immunohistochemistry for TDP-43 in an anterior horn of the spinal cord in SCA2 has demonstrated three different expression patterns: 'intranuclear' 'nuclear with inclusions' and 'cytoplasmic'. These results show that the translocation of the TDP-43 protein in a nerve cell may play an important role of the cell death of SCD.

Research Products

• [Journal Article] Neuropathological staging of spinocerebellar ataxia type 2 by semiquantitative 1C2-positive neuron typing Nuclear translocation of cytoplasmic 1C2 underlies disease progression of spinocerebellar ataxia type 2. (2014)
  • Author(s): Koyano S, Yagishita S, Kuroiwa Y, Tanaka F, Uchihara T.
  • Journal Title: Brain Pathol Volume: 26 Issue: 6 Pages: 599-606
  • DOI: 10.1111/bpa.12146
  • Peer Reviewed
• [Journal Article] Mutations in COQ2 in familial and sporadic multiple-system atrophy the multiple-system atrophy research collaboration (2013)
  • Author(s): Mitsui J, et. al.
  • Journal Title: N Engl J Med Volume: 369 Issue: 3 Pages: 233
  • DOI: 10.1056/nejmoa1212115
  • Peer Reviewed
• [Presentation] 多系統萎縮症と尿酸との関連性 (2013)
  • Author(s): 児矢野繁、鈴木ゆめ、田中章景
  • Organizer: 第54回神経学会総会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
• [Presentation] SCA2とALSにおける共通結合蛋白(TDP-43とATXN2) (2011)
  • Author(s): 児矢野繁、黒岩義之、柳下三郎、内原俊記
  • Organizer: 第52回日本神経学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-18