Development of therapeutic strategy for Alzheimer's disease based on axonal regeneration in the brain

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K16288
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: University of Toyama
• Principal Investigator: Yang Ximeng 富山大学, 学術研究部薬学・和漢系, 助教 (80818922)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: アルツハイマー病 / 軸索再伸長 / 記憶回復 / Diosgenin / SPARC / Galectin-1

Outline of Final Research Achievements

This study aimed to develop a new therapeutic strategy for Alzheimer's disease (AD) by regenerating axons (one of the neurites) in the brain. We demonstrated that axons projecting from the hippocampus to the prefrontal cortex were atrophied in AD model (5XFAD) mice; however, diosgenin administration significantly promoted axonal regeneration in this neural circuit. In addition, SPARC and Galectin-1 were identified as responsible proteins for accurate axonal re-innervation in the brain. We also confirmed that axonal regeneration in the brain directly related to memory recovery in 5XFAD mice, suggesting the importance of repairing axons in AD treatment.

Free Research Field

神経薬理学、神経科学

Academic Significance and Societal Importance of the Research Achievements

これまでの脳科学上の常識では、成体脳の軸索は再伸長することが難しいと考えられてきたが、本研究ではアルツハイマー病脳内の軸索が再伸長できる根拠と、本現象を担う責任タンパク質（SPARC, Galectin-1）を明らかにし、さらにこれを誘発できる薬物ジオスゲニンを初めて見出した。また、脳内での軸索再伸長が確かに記憶回復をもたらすことも明らかにした。これらは、脳内の軸索再伸長がアルツハイマー病をはじめとした神経変性疾患に対する新規治療戦略になりうることを示唆する知見である。