α-Syn conformers, oligomers, protofibrils, and fibrils have been shown to activate the nucleotide-binding oligomerization domain containing protein 3 and leucine-rich repeat-containing receptors (NLRP3) inflammasome, which is the first line of defense against non-self-pathogens, indicating an innate immune response at the beginning of PD pathogenesis. The gene discussed is NLRP3; the disease is Parkinson disease.