The role of inositol hexakisphosphate kinases for the onset mechanism of amyotrophic lateral sclerosis

• Project/Area Number: 25430014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Tokai University
• Principal Investigator: NAGATA Eiichiro 東海大学, 医学部, 准教授 (00255457)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 筋萎縮性側索硬化症 / イノシトール6リン酸キナーゼ2 / 脊髄前角細胞 / TDP-43 / トランスジェニックマウス

Outline of Final Research Achievements

To address the role of IP6K2 in amyotrophic lateral sclerosis (ALS), we investigated the expression level of IP6K2, employing G93A mutant human superoxide dismutase-1 over-expressing transgenic mice (Tg mice) as ALS. The specimens of spinal cords were obtained from Tg mice and week age-matched wild-type mice. We investigated the expression levels of IP6K2 on the genes and proteins in Tg and wild-type mice. The gene expression level of IP6K2 in Tg mice at postnatal 17 weeks around the onset of ALS symptoms was lower compared to that of wild-type mice, while at postnatal 12 weeks before the symptoms of ALS it was signifivantly higher compared to wild-type mice. In the immunohistochemistry against IP6K2, it was stained in the cytoplasm in Tg mice during each week-old. These findings suggest that IP6K2 might be activated in Tg mice before the onset of ALS. IP6K2 might be a pre-symptomatic biomarker for ALS.

Research Products

• [Journal Article] Inositol Hexakisphosphate Kinase 2 Promotes Cell Death in Cells with Cytoplasmic TDP-43 Aggregation. (2015)
  • Author(s): Nagata E, Nonaka T, Moriya S, Fujii N, Okada Y, Tsukamoto H, Itoh J, Okada C, Satoh T, Arai T, Hasegawa M, Takizawa S.
  • Journal Title: Molecular Neurobiology Volume: 6
  • Peer Reviewed / Open Access
• [Presentation] 筋萎縮性側索硬化症（ALS）におけるイノシトール6リン酸キナーゼの役割 (2015)
  • Author(s): 永田栄一郎
  • Organizer: 東海大学総合医学研究所第18回公開研究報告会
  • Place of Presentation: 東海大学医学部（伊勢原）
  • Year and Date: 2015-03-06
• [Presentation] イノシトール6リン酸キナーゼ2は筋萎縮性側索硬化症患者脊髄おいて細胞死を促進する
  • Author(s): 永田栄一郎
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
• [Presentation] ALSモデルマウスのけるイノシトール6リン酸キナーゼ2の病態への関連性について
  • Author(s): 森谷祐介
  • Organizer: 東海大学総合医学研究所発表会
  • Place of Presentation: 東海大学医学部（伊勢原）
• [Presentation] Inositol hexakisphosphate kinase 2 is one of the candidate molecules as diagnostic marker for amyotrophic lateral sclerosis.
  • Author(s): E. Nagata
  • Organizer: Neuro2013
  • Place of Presentation: 京都