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α-Synuclein inhibitors and degraders act on a presynaptic protein that aggregates in Parkinson's disease. α-Synuclein (SNCA) is a small, natively unfolded protein that associates with membranes and synaptic vesicles. In 1997 a point mutation in its gene was found in families with inherited Parkinson's disease. The same year it was detected as a major component of Lewy bodies, the protein inclusions typical of the disease. Misfolded α-synuclein forms oligomers and amyloid fibrils, which are studied in aggregation assays, neuronal cells and transgenic animals. SynuClean-D and PBT434 mesylate are listed as aggregation inhibitors, minzasolmin as an oligomerization inhibitor and CLR01 sodium as a molecular tweezer. Proteolysis-targeting chimeras (PROTACs) such as PROTAC α-synuclein degrader 3 direct the protein to proteasomal degradation.
