α-Synuclein belongs to the Synuclein family of proteins containing three other members (β-synuclein, γ-synuclein and synoretnin). α-Synuclein is a highly conserved acidic protein that is concentrated mainly in presynaptic axon terminals.

The gene encoding α-synuclein is known as SNCA or PARK1. α-Synuclein, together with other members of its family, lacks typical secondary structure. In its primary structure, α-synuclein is characterized by seven imperfect 11-residue repeat sequences that are predicted to form five amphipatic helices on the amino terminal half. The acidic, glutamate rich carboxy-terminal region remains unstructured even in the presence of membranes. α-Synuclein helices 1-4 are predicted to associate with lipid vesicles while helix 5 would be responsible for protein-to-protein interaction. The protein interacts and with DAT, the dopamine transporter, and thus is involved in dopamine signaling. Under pathological conditions, α-synuclein can undergo conformational changes leading to protein aggregation and deposition.

α-Synuclein shares structural homology with the 14-3-3 family of chaperon proteins and its expression is upregulated during periods of accelerated neuronal activity and plasticity thus suggesting it might be functioning as a molecular chaperon capable of binding to other intercellular proteins.

α-Synuclein has been implicated in the pathophysiology of Parkinson’s disease (PD) and Lewy body dementia (DLB). Mutations A30P and A3T are associated with PD while mutation E46K has been linked to DLB. These mutated α-synucleins form fibrils more rapidly than the wild-type protein in aqueous solution¹. α-Synucleins are the major components of Lewy bodies and Lewy neurites in both diseases².