Molecular Pathogenesis of Familial Amyotrophic Lateral SclerosisType 6

• Project/Area Number: 22500335
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Hiroshima Bunkyo Women's University
• Principal Investigator: FUJII Ritsuko 広島文教女子大学, 人間科学部, 教授 (90342716)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 精神・神経疾患の病態と治療 / 脳神経疾患 / 神経科学

Research Abstract

Recently, specific point mutations in C-terminus region of TLS have been identified as a cause of familial amyotrophic lateral sclerosis (FALS) type6. TLS with ALS-related point mutations are prone to aggregate and TLS-deficiency is correlated with defective RNA splicing of specific sets of RNAs. Our iCLIP analysis of TLS-deficient mouse brain and mass spectrometry analysis of TLS-protein complex have indicated that TLS-deficiency may induce mitochondrial stress responses and aberrant RNA metabolism in neurons.

Research Products

• [Journal Article] Expression of NR1 and NR2 splice variants in TLS-deficient mice (2012)
  • Author(s): R.Fujii,N. Nishimura and C. Yamamoto:
  • Journal Title: J. Neurochem Volume: 123(S1) Pages: 120-120
• [Journal Article] Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain (2012)
  • Author(s): B. Rogelj, L.E. Easton, G.K. Bogu, L.W.Stanton, G. Rot, T. Curk, B. Zupan, Y. Sugimoto, M. Modic, N. Haberman, J. Tollervey, R.Fujii, T. Takumi, C E. Shaw and J. Ule
  • Journal Title: Sci. Rep Volume: 2 Issue: 1 Pages: 1-10
  • DOI: 10.1038/srep00603
  • Peer Reviewed
• [Journal Article] RNA binding region of TLS interacts with nucleoporin. (2012)
  • Author(s): R.Fujii and T. Takumi
  • Journal Title: J. Neurochem. Volume: 123 (S1) Pages: 60-60
• [Journal Article] RNA binding protein TLS and neuronal disorders. (2010)
  • Author(s): R.Fujii
  • Journal Title: Journal of the Society for Food Nutrition Volume: 27/28 Pages: 2-5
• [Journal Article] 精神神経疾患とRNA結合タンパクTLS (2010)
  • Author(s): 藤井律子
  • Journal Title: 広島文教食物栄養研究会誌 Volume: 27/28(合併号) Pages: 2-5
• [Presentation] Expression of NR1 and NR2 splice variants in TLS-deficient mice. (2012)
  • Author(s): R.Fujii,N. Nishimura and C. Yamamoto:
  • Organizer: 日本神経化学会
• [Presentation] RNA bindingregion of TLS interacts with nucleoporin. (2012)
  • Author(s): R.Fujii and T. Takumi
  • Organizer: 日本神経化学会
• [Presentation] Expression of NR1 and NR2 splice variants in TLS-deficient mice (2012)
  • Author(s): R.Fujii
  • Organizer: APSN/the Japanese Society for Neurochemistry
  • Place of Presentation: Kobe,Japan
• [Presentation] RNA binding region of TLS interacts with nucleoporin (2012)
  • Author(s): R.Fujii
  • Organizer: APSN/the Japanese Society for Neurochemistry
  • Place of Presentation: Kobe,Japan
• [Book] Chapter 9 Animal Models of ALS. Animal models for neurodegenerative disease (2011)
  • Author(s): R.Fujii and T. Takumi
  • Publisher: RSC Publishing, Cambridge, UK
• [Book] Chapter 9 Animal models of ALS.J.Avila, J.J.Lucas and F.Hernandez ed. : Animal models for neurodegenerative disease.ISBN 978-1-84973-275-8 (2011)
  • Author(s): *R.Fujii, T.Takumi *corresponding author
  • Publisher: RSC Publishing (Cambridge, UK)
• [Book] Animal Models for Neurodegenerative Disease RSC Drug Discovery Series No.6 : Chapter 9 Animal Models for ALS (2011)
  • Author(s): R.Fujii, T.Takumi
  • Total Pages: 37
  • Publisher: The Royal Society of Chemistry (UK)