Rodent and cell culture studies suggest that HMGB1 (which activates TLR4, RAGE, and Mac1), S100B (primarily of astrocyte origin, also a RAGE ligand), and oligomeric ASYN (a ligand for TLR2 and CD11b) contribute to chronic microglial activation in PD [31,34,35,36,37,38,39,40,41,42,43]. This evidence concerns the gene HMGB1 and Parkinson disease.