Formation and function of primary cilia in cytotoxic astrocyte in neuroinflammation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06837
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Keio University (2023); Nara Institute of Science and Technology (2021-2022)
• Principal Investigator: ITOH Hiroshi 慶應義塾大学, 薬学部(芝共立), 客員教授 (10183005)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: アストロサイト / 一次繊毛 / 神経炎症

Outline of Final Research Achievements

As society enters an era with a growing population of elderly individuals, it becomes increasingly important to elucidate the mechanisms underlying the onset of Alzheimer's disease and Parkinson's disease. It has been revealed that chronic neuroinflammation is involved in the onset of dementia; however, many aspects of the involvement of astrocytes remain unclear. Recently, diversity among astrocytes and the presence of reactive astrocytes exhibiting cytotoxicity have been discovered. In this study, we aimed to clarify the role of primary cilia, which function as cellular antennae, in the generation of cytotoxic astrocytes during neuroinflammation. The results indicated that primary cilia elongate during neuroinflammation and contribute to the generation of cytotoxic astrocytes, which are involved in cognitive impairment.

Free Research Field

分子薬理学

Academic Significance and Societal Importance of the Research Achievements

神経炎症は、アルツハイマー病やパーキンソン病などの進行性神経変性疾患で起こり病態の進行に寄与していると考えられている。本研究により神経炎症時にみられる神経細胞障害性アストロサイトの誘導および神経細胞死、さらに認知機能低下の一端にアストロサイトの一次繊毛が大事な働きをすることが明らかになった。神経炎症時にアストロサイトの一次繊毛の機能を抑制することにより、進行性の神経変性疾患を抑制できる可能性が判明した。本研究成果は現在画期的な治療薬が存在しないこれらの疾患の標的として、アストロサイトの一次繊毛に的を絞った治療薬探索に向けた第一歩となることが大いに期待される。