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Salidroside ameliorates Parkinson's disease by inhibiting NLRP3-dependent pyroptosis.

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-1?, 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) in vivo, MPTP-induced PC-12 and LPS-induced BV2 in vitro. We found that Sal could ameliorate MPTP-induced PD symptoms and reduce the levels of IL-1?, 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-1? and pro-IL-18 by inhibiting TLR4/MyD88/NF-?B 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.

SUBMITTER: Zhang X

PROVIDER: S-EPMC7288953 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Salidroside ameliorates Parkinson's disease by inhibiting NLRP3-dependent pyroptosis.

Zhang Xue X Zhang Yiming Y Li Rui R Zhu Lingpeng L Fu Buqing B Yan Tianhua T

Aging 20200519 10

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 p ...[more]

PMID: 32432571

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Dataset Information

Salidroside ameliorates Parkinson's disease by inhibiting NLRP3-dependent pyroptosis.

Publications

Salidroside ameliorates Parkinson's disease by inhibiting NLRP3-dependent pyroptosis.

Similar Datasets

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