Role of NLRP3 Inflammasome in Parkinson's Disease and Therapeutic Considerations

Parkinson's disease (PD) is the second most common neurodegenerative disease, with two main pathological features: misfolded alpha-synuclein protein accumulation and neurodegeneration. Inflammation has recently been identified as a contributor to a cascade of events that may aggravate PD pathology. Inflammasomes, a group of intracellular protein complexes, play an important role in innate immune responses to various diseases, including infection. In PD research, accumulating evidence suggests that alpha-synuclein aggregations may activate inflammasomes, particularly the nucleotide-binding oligomerization domain-leucine-rich repeat-pyrin domain-containing 3 (NLRP3) type, which exacerbates inflammation in the central nervous system by secreting proinflammatory cytokines like interleukin (IL)-18 and IL-1 beta. Afterward, activated NLRP3 triggers local microglia and astrocytes to release additional IL-1 beta. In turn, the activated inflammatory process may contribute to additional alpha-synuclein aggregation and cell loss. This review summarizes current research evidence on how the NLRP3 inflammasome contributes to PD pathogenesis, as well as potential therapeutic strategies targeting the NLRP3 inflammasome in PD.

Automated summary

This review summarizes the role of the NLRP3 inflammasome in the pathogenesis of Parkinson's disease (PD) and potential therapeutic strategies targeting the NLRP3 inflammasome in PD.