α-synuclein

α-Synuclein is a presynaptic neuronal protein that associates with synaptic vesicle membranes and participates in the regulation of neurotransmitter release, vesicle trafficking, and synaptic vesicle organization^[1][2][3]. Mechanistically, α-synuclein binds membrane phospholipids, promotes vesicle clustering, and facilitates processes linked to synaptic vesicle integrity and SNARE-dependent neurotransmission, thereby contributing to normal synaptic function^[1][2][4]. Dysregulation of these physiological activities is closely associated with abnormal protein folding, oligomerization, and fibrillization, which disrupt cellular homeostasis and impair pathways including vesicle trafficking, lysosomal function, and mitochondrial integrity^[5][6][7]. In disease contexts, α-synuclein is the major constituent of Lewy bodies and represents a central pathogenic factor in Parkinson’s disease and related synucleinopathies, where aggregated species accumulate in vulnerable neuronal populations and contribute to progressive neurodegeneration^[6][8][9]. Experimental studies further indicate that abnormal or mutant α-synuclein alters lipid homeostasis and presynaptic trafficking, providing mechanistic links between protein aggregation and neuronal dysfunction^[7]. Compared with the related synuclein family members β-synuclein and γ-synuclein, α-synuclein has received particular attention because its aggregation propensity and pathological deposition are directly associated with Lewy body pathology and disease progression^[8][9]. For experimental applications, α-synuclein aggregation models, oligomer-based assays, and aggregation-targeting modulators are widely used to investigate pathogenic mechanisms and evaluate potential therapeutic strategies for synucleinopathies^[5][10].