About this Research Topic
α-Synuclein (α-Syn) is a highly abundant presynaptic protein and is expressed throughout the central nervous system. Abnormal amyloid aggregation of α-Syn into Lewy body is the hallmark of Parkinson's and other Lewy body diseases. Missense mutations of α-Syn, and duplications or triplications of SNCA gene lead to early onset Parkinson's disease (PD).
α-Syn contains three regions, including the N-terminal lipid-binding motif, the central non-amyloid component (NAC) region and the C-terminal region. In aqueous solution, α-Syn features an intrinsically disordered conformation and is prone to self-assembly via its NAC into amyloid oligomers and fibrils closely related to pathogensis in PD. While, in the presence of membrane or lipid molecules, α-Syn adopts partially α-helical conformation and binds to the membrane via its N-terminal. Membrane binding was believed to be essential in mediating α-Syn physiological function in synaptic vesicle (SV) trafficking (e.g. SV clustering, docking and fusion). However, the binding mode is highly diverse depending on the lipid compositions and other factors, which in turn influences its function in SV trafficking. Moreover, different lipid molecules exhibit distinct or even opposite effects on mediating multimerization and aggregation of α-Syn. Disruption of lipid homeostasis was found to be associated with α-Syn aggregation in Parkinsonisms. Thus, comprehensive studies of α-Syn and membrane interaction is of great importance not only in understanding its physiological function during SV trafficking, but also in revealing how membrane and lipids molecules regulate self-assembly of α-Syn in normal and disease conditions.
In this Research Topic, the membrane association of α-Syn will be covered from molecular mechanism to physiological functions, and pathological aggregation in disease condition. We welcome any types of contributions such as original research, review, and perspective.
Keywords: alpha-synuclein, membrane, multimerization, synapse trafficking, Parkinson’s disease
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