Investigation of alpha-synuclein associated synaptic dysfunction by unraveling the molecular mechanisms using 3D brain organoid model

通过使用 3D 脑类器官模型揭示分子机制来研究 α-突触核蛋白相关的突触功能障碍

• 批准号: 21K06896
• 负责人: Jo Junghyun
• 金额: $ 2.66万
• 依托单位: Okinawa Institute of Science and Technology Graduate University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K06896/
• 关键词: Parkinson's disease; Embryonic stem cell; Organoid; SNCA; GBA1; alpha-synuclein; Pluripotent stem cell; Glucocerebrosidase

As a Principal Investigator, Dr. Junghyun Jo decided to discontinue the KAKENHI project in early January 2022 because he resigned from his position at OIST, there were not much research achievements for about 10 months. Following the Specific Aim 1 for Year 1 and 2, he has successfully created hMLO-hSLO fusion organoid using wildtype and GBA1 human embryonic stem cells that showed reciprocal nigro-striatal and striato-nigral projections. Using the fusion organoid, he has validated the formation of synapses between dopaminergic neurons and GABAergic neurons at each area. Also, he confirmed the formation of alpha-synuclein aggregation in the fusion organoids.

作为首席研究员，Junghyun Jo博士于2022年1月初决定停止KAKENHI项目，因为他辞去了OIST的职务，大约10个月没有太多的研究成果。在第1年和第2年的特定目标1之后，他成功地使用野生型和GBA 1人胚胎干细胞创建了hMLO-hSLO融合类器官，这些细胞显示出相互的黑质-纹状体和黑质-纹状体投射。使用融合类器官，他验证了多巴胺能神经元和GABA能神经元之间在每个区域形成突触。此外，他证实了融合类器官中α-突触核蛋白聚集的形成。