Targeting novel regulated cell death：Ferroptosis, pyroptosis, and autophagy in sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE), a common neurological complication of sepsis, is a heterogenous complex clinical syndrome caused by the dysfunctional response of a host to infection. This dysfunctional response leads to excess mortality and morbidity worldwide. Despite clinical relevance with high incidence, there is a lack of understanding for its both its acute/chronic pathogenesis and therapeutic management. A better understanding of the molecular mechanisms behind SAE may provide tools to better enhance therapeutic efficacy. Mounting evidence indicates that some types of non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis, and autophagy, contribute to SAE. Targeting these types of RCD may provide meaningful targets for future treatments against SAE. This review summarizes the core mechanism by which non-apoptotic RCD leads to the pathogenesis of SAE. We focus on the emerging types of therapeutic compounds that can inhibit RCD and delineate their beneficial pharmacological effects against SAE. Within this review we suggest that pharmacological inhibition of non-apoptotic RCD may serve as a potential therapeutic strategy against SAE. [Display omitted] • Ferroptosis is involved in the genesis of sepsis-associated encephalopathy. • Pyroptosis is involved in the genesis of sepsis-associated encephalopathy. • Autophagy is involved in the genesis of sepsis-associated encephalopathy. • Inhibiting ferroptosis,pyroptosis, and autophagy as a therapeutic target for SAE. • Small-molecule compounds that inhibit ferroptosis, pyroptosis, and autophagy shed new light on the development of drugs to treat SAE in the future. [ABSTRACT FROM AUTHOR]