Salidroside Ameliorates Parkinson's Disease by Inhibiting NLRP3-dependent Pyroptosis

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 May 21

PMID 32432571

Citations 59

Authors

Xue Zhang

Yiming Zhang

Rui Li

Lingpeng Zhu

Buqing Fu

Tianhua Yan

Affiliations

Soon will be listed here.

Abstract

Parkinson's disease (PD) is a common age-related neurodegenerative movement disorder, which is mainly due to the loss of dopaminergic neurons. Pyroptosis is a new programmed cell death characterized by NLR Family Pyrin Domain Containing 3 (NLRP3)-dependent, IL-1β, IL-18 and Gasdermin D. Salidroside (Sal) has been reported to have neuro-protective effect. However, the roles of pyroptosis and Sal on anti-pyroptosis in PD have not been elucidated. In this study, we tested underlying mechanisms of pyroptosis in PD and neuro-protective effects of Sal. We established 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced C57BL/6J mice and C57BL/10ScNJ (TLR4-deficient mice) , MPTP-induced PC-12 and LPS-induced BV2 . 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.

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