Abstract: Objective To elucidate the regulatory network linking microglial autophagy to NLRP3 inflammation so as to provide a reference for targeted interventions in Parkinson's disease. Methods The pathological mechanisms of Parkinson's disease, activation pathways of the NLRP3 inflammasome, and regulatory mechanisms of cellular autophagy were explored based on literature review. The underlying mechanisms linking microglia-mediated inflammatory responses to autophagy dysfunction were identified and their roles in the onset and progression of Parkinson's disease as well as the current research were summarized. Results Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the abnormal aggregation of α-synuclein. Overexpression of the NLRP3 inflammasome and defects in microglial autophagy are deeply involved in its pathological progression. Currently, there is a lack of systematic integration of the mechanisms of their mutual regulation. Conclusion Excessive activation of the NLRP3 inflammasome and defects in microglial autophagy synergistically exacerbate dopaminergic neuron damage and the pathological spread of α-synuclein, thereby accelerating disease progression. Conversely, activating microglial autophagy can inhibit NLRP3 inflammasome activation and exert neuroprotective effects. The dynamic interactions between these two processes regulate the course of Parkinson's disease, and targeted intervention in this regulatory axis may provide new insights into the clinical prevention and treatment of the disease. The combined formulations of small-molecule NLRP3 inhibitors, natural autophagy modulators, brain-targeted nanodrugs, and cell-specific prodrugs may promise a new sphere of research for the development of novel Parkinson's disease therapeutics.

Key words: Parkinson's Disease, Targeted Drugs, NLRP3 Inflammasome, α-Synuclein, Autophagy, Microglia