Role of VPS13C at organelle contact sites and involvement in dopaminergic neurodegeneration

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16929
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Juntendo University
• Principal Investigator: Ogata Jun 順天堂大学, 医学部, 特任助教 (20825179)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: VPS13C / パーキンソン病 / PLA2G6 / 脂質

Outline of Final Research Achievements

In order to analyze the function of the Parkinson's disease (PD) causative gene, VPS13C, VPS13-EGFP knock-in Drosophila was prepared and its intracellular localization was examined. As a result, accumulation in lipid droplets and lysosomes was observed. Similarly, the PD causative gene PLA2G6 encodes phospholipid lipase A2. Therefore, we thought that the breakdown of lipid homeostasis might be one of the causes of PD. Omics analysis by comprehensive lipid analysis and RNAseq detected changes in several lipid molecular species and lipid-related genes, which partially correlated with several phenotypes.

Free Research Field

神経学

Academic Significance and Societal Importance of the Research Achievements

PDの原因としてマイトファジー制御や小胞輸送制御の異常が考えられる。これらの現象を引き起こす原因として脂質分子、脂質関連遺伝子にフォーカスし、いくつかの候補をリストアップできた。リスク脂質分子種と責任脂質酵素の同定は、食事指導によるPDリスク予防、脂質酵素に対するPDの分子標的薬の探索に繋がると期待される。