Fig. 1

Overview of the pathogenesis of Parkinson's Disease. Various risk factors are involved in the pathogenesis of PD. Inherited as well as acquired gene mutations result in the generation of abnormal proteins. In the neuron, SNCA gene mutations encode an abnormal α-synuclein protein which forms aggregates and accumulates due to abnormal proteostasis mechanisms (UPS and ALP). Mutations in PINK1, PRKN, DJ-1, LRRK2, and PGC-1α are associated with mitochondrial dysfunction, resulting in ATP depletion, oxidative stress, and activation of neuroinflammatory pathways. Environmental chemicals like rotenone directly inhibit mitochondrial complex 1. The resulting DAMPs protein (damage-associated molecular patterns) and other pathologic events like K + efflux and lysosomal damage stimulate the NLRP3 inflammasome activation in the microglia, resulting in the generation of pro-inflammatory cytokines. These cytokines further propagate the inflammation, creating a vicious cycle that ultimately leads to the neuron's demise. DA: Dopaminergic, ALP: Autophagy-lysosomal pathway; UPS: Ubiquitin proteasome pathway; TLR: Toll-like receptor; ROS: Reactive oxygen species