Ketone body-utilizing enzyme as a potential target for prevention and treatment of cognitive impairment

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14908
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Hoshi University
• Principal Investigator: Hasegawa Shinya 星薬科大学, 薬学部, 講師 (60386349)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ケトン体 / 脂質代謝 / 認知機能障害 / 脳・神経系 / コレステロール / トリグリセリド / 高脂肪食

Outline of Final Research Achievements

The pathogenesis of cognitive dysfunction, such as Alzheimer's disease, is still unclear, and its treatment is mainly symptomatic. In this study, we investigated the role of acetoacetyl-CoA synthetase (AACS), a ketone body utilizing enzyme, in the brain and nervous system. We found that AACS regulates genes involved in neural development in the brain and may affect mitochondrial metabolism and neural morphogenesis under the condition of abnormal glucose and lipid metabolism. These results provide new insights into the role of ketone body metabolism in the function of central nervous system and may provide useful basic knowledge regarding new therapeutic and preventive methods for neurodegenerative diseases such as cognitive impairment.

Free Research Field

衛生薬学、栄養代謝学

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー型認知症などの認知機能障害は65歳以上の高齢者において有病率が15%と推定され、認知症と正常の中間に分類される境界型の人と合わせるとその割合は28%に及ぶが、未だ発症機序に不明な点が多く、その治療も対症療法を中心としている。本研究の成果により、未だ着目されていなかったケトン体代謝が神経の正常な発生や発達に関わる可能性が示唆され、認知機能障害などの神経変性疾患の病態を解明するうえで、検討するべき機能を有することが示唆され、予防や治療法に繋がる知見となる可能性が示唆された。