Alpha-synuclein (pathological conformers) (α-syn)

Alpha-synuclein is a 140-amino acid protein primarily expressed in the brain, where it localizes to presynaptic terminals and plays a role in synaptic vesicle trafficking and neurotransmitter release (UniProt P37840). In neurodegenerative disorders known as synucleinopathies, such as Parkinson's disease and Dementia with Lewy bodies, the protein undergoes a conformational shift from a soluble monomer to toxic oligomers and insoluble amyloid fibrils (PubMed: 31515440). These pathological conformers are the primary constituents of Lewy bodies and Lewy neurites, and they are thought to spread through the brain in a prion-like manner, inducing neurotoxicity and cell death (PubMed: 29353461). Therapeutic interventions targeting these conformers include monoclonal antibodies designed to clear extracellular aggregates and small molecules intended to inhibit the aggregation process or stabilize the monomeric form (PubMed: 34635858). Current clinical efforts focus on reducing the burden of these toxic species to slow or halt the progression of neurodegeneration, supported by novel diagnostic tools like the alpha-synuclein seed amplification assay (PubMed: 37161393).

Other names

SNCANon-amyloid component of plaque precursorNACPPARK1PARK4Lewy body proteinPathological alpha-synuclein aggregatesAlpha-synuclein oligomersAlpha-synuclein fibrils

Inhibition of protein aggregation, promotion of autophagic or proteasomal clearance, and neutralization of extracellular seeding species via monoclonal antibodies.