Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson's Disease

According to emerging studies, the excessive activation of microglia and the subsequent release of pro-inflammatory cytokines play important roles in the pathogenesis and progression of Parkinson's disease (PD). However, the exact mechanisms governing chronic neuroinflammation remain elusive. Findings demonstrate an elevated level of NLRP3 inflammasome in activated microglia in the substantia nigra of PD patients. Activated NLRP3 inflammasome aggravates the pathology and accelerates the progression of neurodegenerative diseases. Abnormal protein aggregation of alpha-synuclein (alpha-syn), a pathologically relevant protein of PD, were reported to activate the NLRP3 inflammasome of microglia through interaction with toll-like receptors (TLRs). This eventually releases pro-inflammatory cytokines through the translocation of nuclear factor kappa-B (NF-kappa B) and causes an impairment of mitochondria, thus damaging the dopaminergic neurons. Currently, therapeutic drugs for PD are primarily aimed at providing relief from its clinical symptoms, and there are no well-established strategies to halt or reverse this disease. In this review, we aimed to update existing knowledge on the role of the alpha-syn/TLRs/NF-kappa B/NLRP3 inflammasome axis and microglial activation in PD. In addition, this review summarizes recent progress on the alpha-syn/TLRs/NF-kappa B/NLRP3 inflammasome axis of microglia as a potential target for PD treatment by inhibiting microglial activation.

Automated summary

Recent studies have shown that the excessive activation of microglia and release of pro-inflammatory cytokines play crucial roles in the pathogenesis and progression of Parkinson's disease (PD). The elevated level of NLRP3 inflammasome in activated microglia in the substantia nigra of PD patients exacerbates the pathology and accelerates disease progression. Current therapeutic drugs for PD primarily focus on relieving clinical symptoms, as there are no established strategies to stop or reverse the disease.