Salidroside ameliorates Parkinson's disease by inhibiting NLRP3-dependent pyroptosis
Xue Zhang, Yiming Zhang, Rui Li, Lingpeng Zhu, FU Bu-qing, Tianhua Yan
Abstract
. We found that Sal could ameliorate MPTP-induced PD symptoms and reduce the levels of IL-1β, IL-18 and Gasdermin D, which are main hallmarks of pyroptosis. Further study indicated that Sal alleviated PD through inhibiting NLRP3-dependent pyroptosis. In conclusion, pyroptosis plays a key role in PD and Sal protects dopaminergic neurons by inhibiting NLRP3-dependent pyroptosis through: (1) indirectly reducing the production of NLRP3, pro-IL-1β and pro-IL-18 by inhibiting TLR4/MyD88/NF-κB signaling pathways, (2) directly suppressing pyroptosis through inhibiting TXNIP/NLRP3/caspase-1 signaling pathways. These results indicated that inhibiting pyroptosis or administration of Sal could be a novel therapeutic strategy for PD.