Alpha-synuclein (aggregated) (α-syn (aggregated))

Alpha-synuclein is a small, intrinsically disordered protein primarily located in the presynaptic terminals of neurons, where it plays a crucial role in regulating synaptic vesicle trafficking and neurotransmitter release [1, 2]. In neurodegenerative conditions known as synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, the protein undergoes a pathological transformation from its soluble monomeric state into misfolded oligomers and insoluble fibrils [2, 10]. These aggregated species are the primary components of Lewy bodies and are thought to exert neurotoxic effects by disrupting cellular membranes, impairing mitochondrial function, and inducing neuroinflammation [4, 12]. Furthermore, misfolded alpha-synuclein can propagate between cells in a prion-like manner, seeding the aggregation of endogenous protein in healthy neurons and driving disease progression [7, 17]. Therapeutic strategies targeting this molecule include monoclonal antibodies designed to clear extracellular aggregates, small molecules that inhibit the aggregation process, and antisense oligonucleotides aimed at reducing total protein production [9, 10]. Successful intervention requires high specificity for the pathological aggregated forms to avoid interfering with the protein's essential physiological functions [17].

Other names

SNCANACPNon-amyloid component of plaquesLewy body proteinAlpha-synuclein fibrilsAlpha-synuclein oligomersParkinson disease familial 1PARK1PARK4

Inhibition of alpha-synuclein aggregation, promotion of aggregate clearance via immunotherapy, inhibition of prion-like seeding and cell-to-cell propagation, and reduction of total alpha-synuclein production using antisense oligonucleotides.