The study of the molecular mechanism of polyglutamine disease model mice and search for new therapeutic molecule

• Project/Area Number: 21790845
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Kyushu University
• Principal Investigator: SAKAE Nobutaka Kyushu University, 医学研究院, 神経内科 (80423523)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 神経分子病態学 / 脊髄小脳変性症 / ポリグルタミン病 / モデルマウス / 細胞内輸送機能 / ゴルジ体 / 脳神経疾患 / 細胞内輸送機能異常 / ユビキチン・プロテアソーム / 神経化学 / 神経病理学

Research Abstract

Using the expanded 155 polyglutamine overexpression transgenic mice, we analyzed the molecular mechanism of the mice from the early to end stage of the clinical course by sequential western blot analysis and immunofluorescence study. We revealed that the fragmentation of Golgi apparatus were occurred in early stage of the Tg mice. Further, we identified one of the Golgi related molecule was increased in protein expression level and the localization was different compared to the littermate NT mice at early stage.

Research Products

• [Journal Article] Apomorphine treatment in Alzheimer mice promoting amyloid-β degradation. (2011)
  • Author(s): Himeno E, Ohyagi Y, Ma L, Nakamura N, Miyoshi K, Sakae N, Motomura K, Soejima N, Yamasaki R, Hashimoto T, Tabira T, LaFerla FM, Kira J.Ann Neurol
  • Journal Title: 69(2) Pages: 248-256
• [Journal Article] Apomorphin treatment in Alzheimer mice promoting amyroid-b degradation (2011)
  • Author(s): Himeno E, Ohyagi Y, Ma L, Nakamura N, Miyoshi K, Sakae N, et al
  • Journal Title: Annals of Neurology Volume: 69(2) Pages: 248-256
  • Peer Reviewed
• [Journal Article] Alcohol drinking and risk of Parkinson's disease: a case-control study in Japan. (2010)
  • Author(s): Fukushima W, Miyake Y, Tanaka K, Sasaki S, Kiyohara C, Tsuboi Y, Yamada T, Oeda T, Miki T, Kawamura N, Sakae N, Fukuyama H, Hirota Y, Nagai M
  • Journal Title: Fukuoka Kinki Parkinson's Disease Study Group.BMC Neurol. Nov 5;10:111.
• [Journal Article] Phenotypic spectrum of hereditary neuralgic amyotrophy caused by the SEPT9 R88W mutation. (2010)
  • Author(s): Ueda M, Kawamura N, Tateishi T, Sakae N, Motomura K, Ohyagi Y, Kira JI.
  • Journal Title: J Neurol Neurosurg Psychiatry. Jan;81(1) Pages: 94-96
• [Journal Article] Case-control study of risk of Parkinson's disease in relation to hypertension, hypercholesterolemia, and diabetes in Japan. (2010)
  • Author(s): Miyake Y, Tanaka K, Fukushima W, Sasaki S, kiyohara C, Tsuboi Y, Sakae N, et al
  • Journal Title: J Neurol Sci Volume: 293 Pages: 82-86
  • Peer Reviewed
• [Journal Article] Increase in p53 protein levels by presenilin 1 gene mutations and its inhibition by secretase inhibitors. (2009)
  • Author(s): Ma L, Ohyagi Y, Miyoshi K, Sakae N, et al
  • Journal Title: J Alzheimers Dis. 16 Pages: 565-575
  • Peer Reviewed
• [Journal Article] Enhancement of activation of caspases by presenilin 1 gene mutations and its inhibition by secretase inhibitors. (2009)
  • Author(s): Miyoshi K, Ohyagi Y, Sakae N, Motomura K, Ma L, et al
  • Journal Title: J Alzheimers Dis. 16 Pages: 551-564
  • Peer Reviewed
• [Journal Article] Phenotypic spectrum of hereditary neuralgic amyotrophy caused by the SEPT9R88W mutation (2009)
  • Author(s): Ueda M, Kawamura N, Tateishi T, Sakae N, Motomura K, Ohyaei Y, et al
  • Journal Title: J Neurol Neurosurg Psychiatry 81 Pages: 94-96
  • Peer Reviewed
• [Presentation] Analysis of the MJD/SCA3 Tg mice from the view of neuronal dysfunction (2010)
  • Author(s): 栄信孝
  • Organizer: Society for Neuroscience 40th Annual Meeting 2010
  • Place of Presentation: San Diego(米国)
  • Year and Date: 2010-11-14
• [Presentation] 運動失調症における細胞内輸送機能の検討 (2010)
  • Author(s): 栄信孝
  • Organizer: 日本神経学会総会
  • Place of Presentation: 東京国際フォーラム(東京都)
  • Year and Date: 2010-05-21
• [Presentation] 運動失調症の病態機序における細胞内輸送機能の検討 (2010)
  • Author(s): 栄信孝、他
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-20
• [Presentation] A study of the mechanism of spinocerebellar ataxia from the view of neuronal dysfunction (2009)
  • Author(s): 栄信孝、大八木保政、吉良潤一
  • Organizer: 39^<th> Neuroscience meeting
  • Place of Presentation: Chicago
  • Year and Date: 2009-10-17
• [Presentation] A study of the mechanism of spinocerebellar ataxia from the view of neuronal dysfunction (2009)
  • Author(s): Sakae N, et, al.
  • Organizer: 39th Annual Meetings of Society for Neurosciences
  • Place of Presentation: Chicago USA
  • Year and Date: 2009-10-03
• [Presentation] Machado-Joseph 病(MJD)における細胞内輸送機能の検討 (2009)
  • Author(s): 栄信孝、他
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-21
• [Presentation] 運動失調症における細胞内輸送機能検討 (2009)
  • Author(s): 栄信孝、大八木保政、吉良潤一
  • Organizer: 日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-20