α-synuclein Aggregation

α-synuclein is a presynaptic neuronal protein linked to nerve-terminal function and membrane remodeling^[1]. It regulates mature synapses by maintaining distinct synaptic vesicle pools, and it supports neurotransmitter release through synaptic vesicle binding, vesicle clustering, and SNARE-complex assembly^[2][3]. Mechanistically, lipid surfaces shift α-synuclein from an intrinsically disordered state toward membrane-bound helical conformations, while partially folded, oligomeric, fibrillar, and amorphous states define aggregation pathways^[4]. In disease models, misfolded α-synuclein accumulates in Lewy bodies and Lewy neurites, which characterize Parkinson’s disease and related synucleinopathies^[4][5]. Compared with related isoforms, β-synuclein and γ-synuclein show reduced synaptic vesicle affinity and can reduce α-synuclein vesicle binding through heteromerization^[3]. β-synuclein also inhibits α- and γ-synuclein fibrillation at high molar ratios, whereas α-synuclein shows the strongest aggregation propensity among human synucleins^[6]. For experimental applications, biologically representative vesicle mimics and lipid-coated nanoparticles help analyze α-synuclein membrane binding under controlled size, rigidity, and lipid-composition conditions^[7].