While α-syn pathology undoubtedly plays an important role in PD progression and is associated mechanistically with inflammasome and caspase-1 activities14,37 as well as microglia-mediated dopaminergic neurodegeneration21, Lewy body/Lewy neurite pathology per se does not always correlate with neurodegeneration or loss of motor function87; moreover, it is not unique to PD, as other synucleinopathies like DLB and MSA also display α-syn pathology but in brain regions other than the SNpc45,138. This evidence concerns the gene CASP1 and Parkinson disease.