Function of complement factors in the neuropathogenesis of prion disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08070
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: Yamasaki (Hasebe) Rie (長谷部理絵) 北海道大学, 遺伝子病制御研究所, 助教 (70431335)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: プリオン病 / 補体因子 / 神経病態

Outline of Final Research Achievements

Function of the complement factors in the neuropathogenesis of prion disease still remains unclear, although the expression of complement factors is up-regulated from the early stage of the disease. The results of the current study suggest that complement factor C1q expressed by microglia increased the permeability of plasma membrane of neurons via p38 MAPK pathway, and up-regulated activation of astrocytes both in vivo mouse model and in a primary culture system of neurons and glia, The influence of C1q was valid in the early and middle stage of prion infection, however, there was no influence in the clinical and termimal stage of the disease. These results suggest that complement factor C1q may work as a transmitter among neurons and glia that influence the neuropathogenesis of prion disease.

Free Research Field

神経病理

Academic Significance and Societal Importance of the Research Achievements

先行研究により、補体因子はプリオンが末梢から中枢神経系に侵入する際に重要であることが報告されていたが、神経病態形成における補体因子の機能は不明であった。本研究の成果より、補体因子がプリオン感染初期から中期にかけて病態進行に影響を与えることが明らかとなった。補体因子C1qの機能として、神経細胞の細胞膜の透過性を変化させること、アストロサイトの活性化状態を変化させことが発見された。補体因子は神経細胞でのPrPScの増殖を制御することから、本研究の成果は新たな治療薬の開発につながることが期待される。