Therapeutics: Caspase-1 (CASP1); α-synuclein (SNCA)

Patient sample and cell culture studies suggest inhibiting CASP1 could help treat PD. In postmortem brain tissue samples from PD patients, CASP1 was highly expressed in Lewy bodies. In a human dopaminergic cell line, a tool compound that activates the inflammasome increased CASP1 activity, levels of truncated α-synuclein and α-synuclein aggregation and decreased viability compared with no treatment. Also in the tool compound-treated cell line, shRNA targeting CASP1 or the CASP1 inhibitor VX-765 increased viability compared with scrambled shRNA or vehicle. Next steps could include testing CASP1 inhibition in animal models of PD...