Progressive Decrease in the Level of YAPdeltaCs, Prosurvival Isoforms of YAP, in the Spinal Cord of Transgenic Mouse Carrying a Mutant SOD1 Gene

• Project/Area Number: 23790992
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Okayama University
• Principal Investigator: MORIMOTO Nobutoshi 岡山大学, 岡山大学病院, 助教 (60598556)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: ALS / 筋萎縮性側索硬化症 / TRIAD / 第4の細胞死 / YAPdeltaC / リン酸化p73

Research Abstract

Although amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease, the mechanism underlying motor neuron death has not yet been fully clarified. Recently, it was found that general transcriptional repression induces slowly progressive atypical cell death associated withthe shift of balance between YAPdeltaCs as prosurvival factors and activated p73 promoting apoptosis. This type of neuronal death was named transcriptional repression-induced atypical death (TRIAD). Therefore, to investigate possible relationships between the mechanism of motor neuron death in ALS and TRIAD, G93ASOD1 transgenic mice (Tg) were examined as an ALS model. The levels of YAPdeltaCs in the spinal cords of Tg mice decreased with disease progression. Also, the ratio of phosphorylated p73 to total p73 increased during the late symptomatic stage in Tg mice. These results suggest that the progressive decrease in the levels of YAPdeltaCs and the relative increase in phosphorylation of p73 over the time course are correlated with disease progression inALS model animals.

Research Products

• [Journal Article] Frontal dysfunctions of ALS-PBP patients in relation to their bulbar symptoms and rCBF decline. (2012)
  • Author(s): Nobutoshi Morimoto
  • Journal Title: Journal of the Neurological Sciences Volume: 319(1-2) Issue: 1-2 Pages: 96-101
  • DOI: 10.1016/j.jns.2012.04.020
  • Peer Reviewed
• [Journal Article] Effect of mitochondrial transcription factor a overexpression on motor neurons in amyotrophic lateral sclerosis model mice (2012)
  • Author(s): Morimoto, N., Miyazaki, K., Kurata, T., Ikeda, Y., Matsuura, T., Kang, D., Ide, T., Abe, K.
  • Journal Title: J Neurosci Res Volume: 90 Issue: 6 Pages: 1200-12008
  • DOI: 10.1002/jnr.23000
  • Peer Reviewed
• [Journal Article] Correlation of cerebral spinal fluid pH and HCO3- with disease progression in ALS (2011)
  • Author(s): Morimoto K, Nagai M, Obta Y, Miyazaki K, Kurata T, Morimoto M, Murakami T, Takehisa Y, Ikeda Y, Kamiya T, Abe K
  • Journal Title: J Neurol Sci Volume: 37 Issue: 1-2 Pages: 74-78
  • DOI: 10.1016/j.jns.2011.05.013
  • Peer Reviewed
• [Journal Article] Correlation of cerebral spinal fluid pH and HCO3- with disease progression in ALS. (2011)
  • Author(s): Morimoto N, Nagai M, Ohta Y, Miyazaki K, Kurata T, Morimoto M, Murakami T
  • Journal Title: J Neurol Sci. Volume: 37(1-2) Pages: 74-78
  • Peer Reviewed
• [Presentation] 新しい ALS/SCA crossroad mutation Asidan (SCA36) の嚥下障害 (2012)
  • Author(s): 第53回神経学会総会(東京) 森本展年、佐藤恒太、宮崎一徳、池田佳生、松浦 徹、阿部康二
  • Organizer: 第53回神経学会総会
  • Place of Presentation: 東京
• [Presentation] 新しいALS/SCA crossroad mutation Asidan (SCA36) の嚥下障害 (2012)
  • Author(s): 森本展年
  • Organizer: 日本神経学会総会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] 岡山大学病院 ALS 患者における認知機能、メタボリックシンドロームの検討 (2011)
  • Author(s): 森本展年、佐藤恒太、倉田智子、池田佳生、松浦 徹、阿部康二
  • Organizer: 第2回日本血管性認知障害研究会 VAS-COG
  • Place of Presentation: 東京
  • Year and Date: 2011-08-20
• [Presentation] タッチパネル式簡易認知症スクリーニング検査を用いた ALS 患者認知機能の検討 (2011)
  • Author(s): 森本展年、佐藤恒太、倉田智子、池田佳生、松浦 徹、阿部康二
  • Organizer: 第30回日本認知症学会学術集会
  • Place of Presentation: 東京
• [Presentation] ALS モデルマウスの脊髄運動ニューロンにおけるα-synuclein、PINK1、DJ-1 の発現について (2011)
  • Author(s): 森本展年宮崎一徳 倉田智子 池田佳生 松浦 徹 阿部康二
  • Organizer: 第52回神経学会総会
  • Place of Presentation: 名古屋
• [Presentation] PROTECTIVE EFFECT OF MITOCHONDRIAL TRANSCROPTION FACTOR A OVEREXPRESSION IN ALS MODEL MICE. (2011)
  • Author(s): Morimoto N, Miyazaki K, Kurata T, Ide T, Ikeda Y, Matsuura T, Abe K.
  • Organizer: 5th SFRR-Asia, 8th ASMRM, 11th J-mit, 2011
  • Place of Presentation: 鹿児島市