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Pyroptosis in stroke-new insights into disease mechanisms and therapeutic strategies

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Abstract

Stroke is a common disease with high mortality and disability worldwide. Different forms of cell deaths, including apoptosis and necrosis, occur in ischemic or hemorrhagic brain tissue, among which pyroptosis, a newly discovered inflammation-related programmed cell death, is generally divided into two main pathways, the canonical inflammasome pathway and the non-canonical inflammasome pathway. Caspase-mediated pyroptosis requires the assembly of inflammasomes such as NLRP3, which leads to the release of inflammatory cytokines IL-1β and IL-18 through the pores formed in the plasma membrane by GSDMD followed by neuroinflammation. Recently, pyroptosis and its relationship with inflammation have attracted more and more attention in the study of cerebral ischemia or hemorrhage. In addition, many inhibitors of pyroptosis targeting caspase, NLRP3, and the upstream pathway have been found to reduce brain tissue damage after stroke. In this review, we mainly introduce the pathology of stroke, the molecular mechanism, and process of pyroptosis, as well as the pivotal roles of pyroptosis in stroke, in order to provide new insights for the treatment of stroke.

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Acknowledgements

This project was supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China (2016ZX09101031) and (2019ZX09301-134) and China Pharmaceutical University “Double First-Class” Construction Technology Innovation Team Project (CPU2018GY23) and (CPU2018GY24) and China Pharmaceutical University “Double First-Class” Construction Graduate Education and Teaching Project (JGYB201909).

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Authors and Affiliations

  1. State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, 210009, China

    Xue Gou, Dan Xu, Fengyang Li, Kai Hou, Weirong Fang & Yunman Li

  2. Department of Pharmacy, Zhongda Hospital, Southeast University, Nanjing, China

    Kai Hou

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  2. Dan Xu
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X. G. and D. X. were involved in collecting information and writing a draft manuscript; F. L. and K. H. performed information consolidation and were involved in modifying article; Y. L. and W. F. were involved in selecting theme. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Weirong Fang or Yunman Li.

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Highlights

• Pyroptosis aggravates brain injury in stroke via the activation of caspase-1/4/5/11.

• Pyroptosis causes inflammation in both cerebral ischemia and intracerebral hemorrhage.

• Caspases, NLRP3, and upstream pathway of pyroptosis are potential therapeutic targets.

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Gou, X., Xu, D., Li, F. et al. Pyroptosis in stroke-new insights into disease mechanisms and therapeutic strategies. J Physiol Biochem 77, 511–529 (2021). https://doi.org/10.1007/s13105-021-00817-w

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