Research Paper Volume 12, Issue 10 pp 9405—9426
Salidroside ameliorates Parkinson's disease by inhibiting NLRP3-dependent pyroptosis
- 1 Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China
- 2 Department of Inspection, The Affiliated Jiangsu Province Hospital of Chinese Medicine of Nanjing University of Chinese Medicine, Nanjing 210009, China
- 3 Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, China
Received: January 18, 2020 Accepted: March 31, 2020 Published: May 19, 2020https://doi.org/10.18632/aging.103215
How to Cite
Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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) 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-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.