Elucidation of Novel Pathogenesis Mechanisms of Neurodegenerative Diseases Focusing on Alterations in Lipid and Iron Metabolism

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K11636
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Teikyo University
• Principal Investigator: Naoki Matsumoto 帝京大学, 薬学部, 助教 (40447834)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脂質代謝 / 鉄代謝 / 神経変性疾患 / ホスホリパーゼ / 翻訳後修飾 / 機能調節

Outline of Final Research Achievements

DDHD1, a lipid-metabolizing enzyme, is an endogenous cannabinoid-producing enzyme and the causative gene for certain types of neurodegenerative diseases. In this study, we showed that DDHD1 is a phosphorylated protein, and that its phosphorylations change DDHD1 function. We identified several responsible kinase and phosphatase, and their targeted phosphorylation sites. We also found several new phenomena in which DDHD1 is associated with iron metabolism. As an example, we found that iron ions reduce the PLA1 activity of DDHD1, and that dysregulation of DDHD1 function leads to a disruption of lipid metabolism homeostasis, leading to the development and exacerbation of various neurodegenerative diseases.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

超高齢社会の到来により、神経変性疾患を含む加齢関連疾患はますます増加の途をたどっている。本研究は、神経変性疾患の病態発現に関わる脂質代謝酵素の新しい機能制御機構を明らかにした。また、この脂質代謝酵素が鉄代謝とクロストークすることを初めて示した。脂質や鉄の代謝異常に着目して、神経変性疾患などの病態発症メカニズムの一端を理解することは、治療や発症予防の対策を講じる上で、極めて有用な情報・知識の集積をもたらす。究極的には健康寿命の延伸につながり、医療費の削減に貢献することが期待できる。