Studies on narcolepsy by orexin/HLA class II complex

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19450
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Osaka University
• Principal Investigator: Arase Hisashi 大阪大学, 微生物病研究所, 教授 (10261900)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Keywords: HLAクラスII / オレキシン / エクソゾーム

Outline of Final Research Achievements

rexin was also found to form a complex with HLA-DQ0602, an allele susceptible to narcolepsy. In contrast, only weak complex formation was observed with the non-sensitive allele. Therefore, it is possible that the cytotoxicity caused by the formation of orexin complexes with HLA-DQ0602 and the interaction with orexin receptors are involved in the survival of orexin-producing cells in patients with narcolepsy. Therefore, we produced orexin-HLA class II complexes and analyzed the cytotoxicity of the complexes. However, no cytotoxicity of the complex was observed in cultured cells. In the future, it will be necessary to analyze the toxicity of the complex using neurons and other cells.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

ナルコレプシーは神経変性疾患の一つであり、オレキシン産生細胞が欠落してしまう疾患であるが、原因は不明である。一方、ナルコレプシーはHLA-DQ0602の遺伝子アリルを持っている人のみが発症する。本研究により、初めてオレキシンがHLA-DQ0602の複合体を形成することが判明した。オレキシン・HLA-DQ0602複合体の詳細な機能までは明らかにできなかったが、今後、オレキシン・HLA-DQ0602複合体の機能の研究を進めることで、ナルコレプシーの発症機構や治療法の開発が可能になることが期待される。