Investigation of abnormal lipid metabolism in Niemann-Pick disease type C based on multiple methodologies

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15699
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Tohoku University
• Principal Investigator: Maekawa Masamitsu 東北大学, 大学病院, 准教授 (70572882)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: ニーマンピック病 / 脂質解析 / LC/MS/MS / 質量分析 / コレステロール / スフィンゴ脂質 / 新規リン脂質 / 化学診断

Outline of Final Research Achievements

In this study, we analyzed the characteristic lipid alterations to Niemann-Pick type C (NPC), the localization of intracellular abnormal metabolism, and the comprehensive variation analysis of lipid metabolism.As a result of structural analysis of Lysosphingomyelin-509 using derivatization method and mass spectrometry method, it was identified as a novel lipid N-palmitoyl-O-phosphocholine-serine.Next, we examined various fluorescent staining reagents for intracellular organelles and confirmed that the intracellular organelle fraction could be traced correctly.For various lipids, we found a characteristic lipid variation in NPC patients using metabolomics analysis methods.

Free Research Field

臨床分析化学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果で、未知脂質lysosphingomyelin-509の構造を決定する過程で、当該分子をN-palmitoyl-O-phosphocholine-serine (PPCS) と明らかにした。PPCSはデータベースに無い新規分子であり、こうした新たな分子を発見できたことは生化学的にも意義が大きい。さらに、網羅的解析からも新たな分子変化が見出されており、今後さらなる解析が期待される。PPCSはニーマンピック病の診断に極めて有用であり、今後の本疾患の診断に役立てられるものと考えられる。