Efficient neuronal regeneration by regulation of protease activity

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06708
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Kawashita Eri 京都薬科大学, 薬学部, 助教 (80509266)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: α2アンチプラスミン / 神経新生 / 移植

Outline of Final Research Achievements

α2-Antiplasmin (α2AP), a member of the serine protease inhibitor (serpin) family, is known as a principal physiological plasmin inhibitor. In this study, we demonstrated that the inhibition of α2AP by the intracerebroventricular injection of an anti-α2AP-neutralizing antibody in WT adult mice enhanced adult hippocampal neurogenesis, and the spatial memory formation and retention. We also found that α2AP is likely to be involved in endogenous neurogenesis after brain injury, and in the engraftment of ES cell-derived cortical neurons transplanted in the cerebral cortex. These findings suggest that α2AP is a potential regulator responsible for functional neurogenesis and reorganization, possibly being useful for efficient neuronal regeneration after brain injury.

Free Research Field

病態生化学

Academic Significance and Societal Importance of the Research Achievements

脳梗塞や認知症、パーキンソン病など根治が困難とされてきた脳神経疾患に対して、再生医療の実現化を目指した神経細胞の移植研究が世界中で行われているが、病態の劇的な改善には、移植した神経細胞の生着性の向上が重要となる。本研究では、α2アンチプラスミン（α2AP）が、生体に本来備わっている神経再生能力や、移植細胞の生着性の向上に関与する可能性を示した。本研究成果は、効果的な神経再生療法の応用に繋がると考えている。