医学创新论坛第66期

CIMR Wednesday Lecture Series

时间：2025年4月16日（周三）下午16:00

地点：首都医科大学基础科研楼北楼二层多功能厅

主持人：

梅林

首都医学科学创新中心

报告人：

郁金泰

教授 / 主任医师

复旦大学附属华山医院

报告题目：

Parkinson's Disease: Original Innovative Target FAM171A2 and Candidate New Drugs

摘要：

Neuronal accumulation and spread of pathological α-synuclein (α-syn) fibrils are key events in Parkinson's disease (PD) pathophysiology. However, the neuronal mechanisms underlying the uptake of α-syn fibrils remain unclear. In this work, we identified FAM171A2 as a PD risk gene that affects α-syn aggregation. Overexpressing FAM171A2 promotes α-syn fibril endocytosis and exacerbates the spread and neurotoxicity of α-syn pathology. Neuronal-specific knockdown of FAM171A2 expression shows protective effects. Mechanistically, the FAM171A2 extracellular domain 1 interacts with the α-syn C terminus through electrostatic forces, with >1000 times more selective for fibrils. Furthermore, we identified bemcentinib as an effective blocker of FAM171A2-α-syn fibril interaction with an in vitro binding assay, in cellular models, and in mice. Our findings identified FAM171A2 as a potential receptor for the neuronal uptake of α-syn fibrils and, thus, as a therapeutic target against PD.

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