α-Synuclein condensation in synaptic vesicle function and synucleinopathies.

Abstract

Research into the crosstalk between α-synuclein (α-syn) and synaptic vesicles (SVs) has gained considerable attention. Notably, the recently discovered liquid-liquid phase separation of α-syn involving SVs is crucial for performing their physiological functions and mediating the transition to pathological aggregates. This review first examines the functional interactions between α-syn and SVs in the context of α-syn's condensation state. It then explores how these interactions become disrupted under pathological conditions, leading to α-syn aggregation and subsequent synaptic dysfunction. Finally, the review discusses the therapeutic potential of targeting α-syn-SV interactions to restore synaptic function in diseased states. By connecting α-syn's physiological roles with its pathological effects, the article aims to shed light on its dual role as both a regulator of SVs and a driver of neurodegeneration.