Role of Reelin/Ephrin pathway for improvement of cognitive function of dementia animals by cell transplantation remedy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07529
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Takai Kenji 聖マリアンナ医科大学, 医学部, 教授 (60121167)
• Co-Investigator(Kenkyū-buntansha): 清水 潤 聖マリアンナ医科大学, 医学部, 教授 (30509964)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 認知症 / hiPS由来神経前駆細胞 / 細胞移植 / Reelin / Eph/ephrin経路 / Reelin分泌細胞 / 海馬治療 / 神経再生

Outline of Final Research Achievements

Hippocampal neural regeneration and Reelin signaling are important for improving cognitive function. Treatment will be performed by transplanting human iPS-derived NSPC (neural stem/progenitor cells), and we explored how Reelin and downstream signaling work. We will investigate the intracellular signaling downstream of Reelin before and after transplantation to explore the mechanism of NSPC fate determination, colonization, and neural circuit formation in recovery. It was likely that NSPC transplantation will reconstruct the neural circuitry of dementia mice. In this process, NSPC produce Reelin, which acts on the host and transplanted cells to phosphorylate downstream Dab1 and Akt, and through downstream intracellular signaling, EphrinB3 activates synapse formation.

Free Research Field

神経疾患のメカニズム

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー型認知症の治療薬として新薬が相次いで承認された。中核症状の治療薬として、塩酸ドネペジルに加えて、同じくアセチルコリンエステラーゼ阻害薬(AChEI)であるガランタミン、リバスチグミンが承認され、さらにN-methyl-D-aspartate(NMDA)受容体拮抗薬であるメマンチンも承認された。いずれも効能・効果は「進行抑制」である。しかし、実際には「進行抑制」だけではない様々な効果を認める。