Role of pericytes in alpha-synuclein accumulation in traumatic brain injury mouse model

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06813
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Fukuoka University
• Principal Investigator: Takata Fuyuko 福岡大学, 薬学部, 准教授 (70412575)
• Co-Investigator(Kenkyū-buntansha): 岩尾 卓朗 福岡大学, 薬学部, 助教 (30846374) ; 道具 伸也 福岡大学, 薬学部, 教授 (60399186)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ペリサイト / 頭部外傷 / パーキンソン病 / alpha-synuclein

Outline of Final Research Achievements

Traumatic brain injury (TBI) produces the secondary damages including Parkinson’s disease (PD). However, it’s unclear the mechanisms by which TBI induces the α-synuclein (αsyn) accumulation in the brain, a responsible factor of the pathology of PD. Our data showed that αsyn expressions were increased in brain of TBI mice. Pericytes in TBI mice and aged pericytes showed the increased expression of PDGFRβ. To evaluate whether PDGFRβ in pericytes is associated with the αsyn degradation, we prepared PDGFRβ knockdown pericytes. The ability of αsyn degradation in PDGFRβ-knockdown pericytes is higher than those in pericytes expressing PDGFRβ, indicating that pericyte activation down-regulated the degradation ability of αsyn in pericytes. Taken together, activation of pericytes induced by TBI and aging might be involved in the accumulation of αsyn in the brain. These finding raise a possibility that pericytes is therapeutic target for preventing the development of PD.

Free Research Field

応用薬剤学

Academic Significance and Societal Importance of the Research Achievements

本研究ではこれまでに注目されていなかった頭部外傷とペリサイトの関係に着目し、パーキンソン病病態責任分子であるα-synucleinの脳内蓄積機構について研究した点に学術的意義がある。パーキンソン病は加齢に伴い発症率が高くなる難治性疾患である。人口の高齢化により患者数は増加することが予測されるため、予防・治療戦略の構築は急務である。新たな治療戦略を提案するための基盤となる知見を得た本研究には社会的意義があると考える。