Authors: Chuchu Wang, Kai Zhang, Bin Cai, Jillian E. Haller, Kathryn E. Carnazza, Jiaojiao Hu, Chunyu Zhao, Zhiqi Tian, Xiao Hu, Daniel Hall, Jiali Qiang, Shouqiao Hou, Zhenying Liu, Jinge Gu, Yaoyang Zhang, Kim B. Seroogy, Jacqueline Burré, Yanshan Fang, Cong Liu, Axel T. Brunger, Dan Li and Jiajie Diao
Nature Cell Biology, 01 July 2024
Researchers studying Parkinson’s disease use Maestro MEA to assess the effects of the α-Syn-VAMP2 interaction on neuronal function and synaptic transmission in vitro.
Aggregation of alpha-synuclein (α-Syn) is a hallmark of Parkinson's disease (PD), and while it is also associated with synaptic vesicle clustering and SNARE complex assembly, it remains unclear if this function is linked to pathological α-Syn aggregation in PD. In this study, scientists investigate the molecular basis of the α-Syn–VAMP2 interaction and explore its impact on the functions of α-Syn, using Axion BioSystems’ noninvasive Maestro Pro multielectrode array (MEA) system to assess the effects of the α-Syn-VAMP2 interaction on neuronal function and synaptic transmission in vitro with no labels or dyes. The results suggest that α-Syn binds to vesicle-associated membrane protein 2 (VAMP2) to promote SNARE complex assembly and synaptic vesicle clustering—a mechanism which may prevent α-Syn aggregation. Overall, the authors conclude that “…this newly discovered non-fusogenic function of VAMP2 in stabilizing α-Syn also holds potential as a platform with which to probe molecular disease mechanisms and identify therapeutic targets for Parkinson’s disease.”
