Exploring inflammasome-mediated neuroimmune regulation in Parkinson's disease and multiple system atrophy

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16277
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: Kyoto University
• Principal Investigator: Takashi Ayaki 京都大学, 医学研究科, 助教 (60749555)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: α-シヌクレイン / ミクログリア / インフラマソーム / NLRP3 / IL1β

Outline of Final Research Achievements

In 2019, we reported behavioral abnormalities in mice with synuclein mutations compared with analysis results in human tissues. In 2020, I reported that inflammation and intracellular inclusion bodies were observed in the muscle pathology of Nakajo Nishimura disease caused by proteasome mutation.
In 2021, we will examine the STING pathway, which is one of the innate immunity, as well as the inflammasome, with regard to neuroinflammatory signals. We reported an increase in STING-related protein-positive microglia and measured interleukin levels in patients' cerebrospinal fluid. Experimental results were reported for the STING pathway with Inoue et al.

Free Research Field

脳神経病理学

Academic Significance and Societal Importance of the Research Achievements

多系統萎縮症、パーキンソン病でのシヌクレイノパチーで、自然免疫系の反応を明らかにした。また他の神経変性疾患（中条西村症候群）での、炎症系シグナルの反応を明らかにした。仮説として、変性疾患における変性タンパクに対する免疫応答機序が想定された。また、社会的には、変性疾患（特にアルツハイマー病）に対するワクチン治療が始まっており、変性疾患に対する免疫応答は治療探求にも重要である。今回の研究結果は、変性疾患に対する免疫応答は治療探求に示唆を与え、貢献する結果であると考えた。