NLRP3 Inflammasome-Mediated Neuroinflammation and Related Mitochondrial Impairment in Parkinson's

Parkinson's disease(PD)is a common neuro-degenerative disorder caused by the loss of dopamine neu-rons in the substantia nigra and the formation of Lewy bod-ies,which are mainly composed of alpha-synuclein fibrils.Alpha-synuclein plays a vital role in the neuroinflamma-tion mediated by the nucleotide-binding oligomerization domain-,leucine-rich repeat-,and pyrin domain-containing protein 3(NLRP3)inflammasome in PD.A better under-standing of the NLRP3 inflammasome-mediated neuroin-flammation and the related mitochondrial impairment during PD progression may facilitate the development of promis-ing therapies for PD.This review focuses on the molecular mechanisms underlying NLRP3 inflammasome activation,comprising priming and protein complex assembly,as well as the role of mitochondrial impairment and its subsequent inflammatory effects on the progression of neurodegenera-tion in PD.In addition,the therapeutic strategies targeting the NLRP3 inflammasome for PD treatment are discussed,including the inhibitors of NLRP3 inflammatory pathways,mitochondria-focused treatments,microRNAs,and other therapeutic compounds.