NLRP3 Inflammasomes in Parkinson’s disease and their Regulation by Parkin

Abstract Chronic inflammation might correlate with the formation of α-synuclein oligomers, subsequently leading to dopaminergic neuronal death in Parkinson’s disease (PD). As major components of chronic inflammation, NOD-like receptor protein 3 (NLRP3) inflammasomes play a crucial role in PD via caspase 1 activation, primarily induced by mitochondrial damage. NLRP3 binds to apoptosis-associated speck-like protein containing a CARD (PYCARD/ASC), and forms inflammasomes in the brain. Inflammasomes act as a platform for caspase 1 to induce interleukin 1 Beta (IL1β) maturation, leading to neuronal pyroptosis. Furthermore, alpha-synuclein, whose abnormal aggregation is the main pathogenesis of PD, also activates NLRP3 inflammasomes. Mutations to PRKN (encoding Parkin) are the most common cause of autosomal recessive familial and sporadic early-onset PD. Evidence has confirmed a relationship between Parkin and NLRP3 inflammasomes. In this review, we summarize the current understanding of NLRP3 inflammasomes and their role in PD progression, and discuss their regulation by Parkin.