Development of a histochemical analytical system for metabolic enzymes of novel brain glycosylated sterols

2020 Fiscal Year Final Research Report

• Project/Area Number: 17KK0147
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Akiyama Hisako 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (80623462)
• Project Period (FY): 2018 – 2020
• Keywords: ステロール / 糖化ステロール / 糖脂質 / グルコシルセラミド分解酵素

Outline of Final Research Achievements

The glucosylceramide-degrading enzyme (GBA) is responsible for the synthesis and degradation of newly found glycosylated sterols (SGs) in the brain. Using a library of GBA inhibitors, I found that GBA exerts various SG metabolic activities using the same active site. I succeeded in detecting SGs in a region of less than 1 mm2 recovered from mouse brain sections using mass spectrometry. Since active GBA can be visualized by fluorescence modified inhibitor, superimposition of the localization of enzyme activity and enzyme reaction products will enable histochemical localization analysis of SG metabolic activities of GBA.

Free Research Field

脂質生化学

Academic Significance and Societal Importance of the Research Achievements

SG群の代謝を担うGBAは、その機能不全がパーキンソン病や小脳失調などの難治性神経変性疾患の原因となる。本研究で提案したGBAのSG代謝活性の組織化学的局在解析法を用いることで、SG代謝が難治性神経変性疾患発症の新たな分子基盤となり得る可能性を検証できるようになるため、本研究成果の学術的・社会的意義は大きい。