C3 and Parkinson disease: In mice, repeated dosing of rotenone caused neuronal loss accompanied by up-regulated microglial CR3 expression; knockout of CR3 prevented the neurodegeneration, suggesting a primary role for complement [134]; however, prevention of complement activation by knocking out C1q or C3 did not reduce neurodegeneration in another toxin-induced PD model, again demonstrating the inconsistencies between studies and models [135,136].