Pyroptosis in neurodegenerative diseases: from bench to bedside

Cell Biol Toxicol. 2023 Dec;39(6):2467-2499. doi: 10.1007/s10565-023-09820-x. Epub 2023 Jul 26.

Abstract

The central nervous system regulates all aspects of physiology to some extent. Neurodegenerative diseases (NDDs) lead to the progressive loss and dysfunction of neurons, which are particularly evident in Alzheimer's disease, Parkinson's disease, and many other conditions. NDDs are multifactorial diseases with complex pathogeneses, and there has been a rapid increase in the prevalence of NDDs. However, none of these diseases can be cured, making the development of novel treatment strategies an urgent necessity. Numerous studies have indicated how pyroptosis induces inflammation and affects many aspects of NDD. Therefore, components related to pyroptosis are potential therapeutic candidates and are attracting increasing attention. Here, we review the role of pyroptosis in the pathogenesis of NDDs and potential treatment options. Additionally, several of the current drugs and relevant inhibitors are discussed. Through this article, we provide theoretical support for exploring new therapeutic targets and updating clinical treatment strategies for NDDs. Notably, pyroptosis, a recently widely studied mode of cell death, is still under-researched compared to other traditional forms of cell death. Moreover, the focus of research has been on the onset and progression of NDDs, and the lack of organ-specific target discovery and drug development is a common problem for many basic studies. This urgent problem requires scientists and companies worldwide to collaborate in order to develop more effective drugs against NDDs.

Keywords: Drug; Inhibitor; Ke-jia Wu and Wan-rong Wang contributed equally to this work.; NLRP3 inflammasome; Neurodegenerative disease; Pyroptosis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Development
  • Humans
  • Neurodegenerative Diseases* / drug therapy
  • Neurodegenerative Diseases* / metabolism
  • Parkinson Disease* / metabolism
  • Pyroptosis