A study for convergent molecular mechanisms underlying epileptic encephalopathy using cortical organoids

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08281
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kyushu University
• Principal Investigator: Sakai Yasunari 九州大学, 医学研究院, 准教授 (10380396)
• Co-Investigator(Kenkyū-buntansha): 中別府 雄作 九州大学, 生体防御医学研究所, 教授 (30180350)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: GNAO1 / 発達性てんかん性脳症 / 分子シグナル / 細胞骨格 / SPTAN1 / タンパク質複合体 / 極性

Outline of Final Research Achievements

Through a proteomic search for Gao, encoded by a developmental and epileptic encephalopathy (DEE)-associated gene GNAO1, we found that the two DEE-associated proteins, Gao and SPTAN1 formed an endogenous complex in the brain. GNAO1-mutated brain organoids showed aberrant expressions of SPTAN1 and other genes associated with axon initial segment and cytoskeletal remodeling. GNAO1 was thus suggested to regulate the process acquiring the functional polarity of differentiating neurons (Akamine S, FASEB J, 2020).

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

異なる二つのDEE関連遺伝子(GaoとSPTAN1)が脳内で複合体を形成し、神経分化に重要な役割を果たすことを初めて明らかにした。これらのタンパク質複合体が脳内で制御する下流分子シグナルをさらに明らかにすることで、難治性てんかんにおける新しい治療標的の同定に寄与できると考えた。