The NLRP3 inflammasome is a potential mechanism and therapeutic target for perioperative neurocognitive disorders

Abstract

Perioperative neurocognitive disorders (PNDs) are frequent complications associated with cognitive impairment during the perioperative period, including acute postoperative delirium and long-lasting postoperative cognitive dysfunction. There are some risk factors for PNDs, such as age, surgical trauma, anesthetics, and the health of the patient, but the underlying mechanism has not been fully elucidated. Pyroptosis is a form of programmed cell death that is mediated by the gasdermin protein and is involved in cognitive dysfunction disorders. The canonical pathway induced by nucleotide oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasomes contributes to PNDs, which suggests that targeting NLRP3 inflammasomes may be an effective strategy for the treatment of PNDs. Therefore, inhibiting upstream activators and blocking the assembly of the NLRP3 inflammasome may attenuate PNDs. The present review summarizes recent studies and systematically describes the pathogenesis of NLRP3 activation and regulation and potential therapeutics targeting NLRP3 inflammasomes in PNDs patients.

Nanotherapeutics for Alleviating Anesthesia‐Associated Complications

“…[32,33] To date, several potential mechanisms underlying POCD have been identified, including neuroinflammation, aggregation of A𝛽 peptides and phosphorylated tau protein, mitochondrial dysfunction, oxidative stress, damage to synapses, and a shortage of neurotransmitter and neurotrophic support, etc. [33,[202][203][204] Remarkably, POCD shares clinical symptoms with early-stage AD, which has pivotal pathogenic hallmarks of A𝛽 plaques and p-tau tangles. [33] Despite the nebulous relationship between POCD and AD, efforts to develop treatments for AD may provide insights into therapeutics for POCD.…”

“…Reproduced with permission. [ 203 ] Copyright 2020, ACS publication. d) Illustration (α) of NIR‐II‐excited catalyst inhibiting Aβ aggregation by photooxygenation; (β) TEM images of Aβ42, and Aβ42+DSM@n‐HOF‐6+NIR‐II; (γ) Representative swimming paths of mice in different groups.…”

“…Scale bars: 300 nm; (𝛾) Representative swimming paths of mice in the probe test. Reproduced with permission [203]. Copyright 2020, ACS publication.…”

Effects of electroacupuncture on postoperative cognitive dysfunction and its underlying mechanisms: a literature review of rodent studies

“…Specifically, the NLRP3 inflammasome is present in microglial cells, while neurons contain the NLRP1 and AIM2 inflammasomes, and astrocytes harbor the NLRP2 inflammasome ( Wang M et al, 2022 ; Wang XF et al, 2022 ). The NLRP3 inflammasome, comprising the NLRP3 protein, pro-caspase-1, and apoptosis-associated speck-like protein containing a CARD (ASC), mediates neuroinflammation that not only directly contributes to the POCD but is also closely associated with high-risk factors for POCD ( Li et al, 2022 ). NLRP3 inflammasome activation occurs in two steps: initiation and activation ( Zhang et al, 2023 ).…”

Giardia VSPAS7 protein attenuates Giardia intestinalis-induced host macrophage pyroptosis

“…It has been reported that Giardia can mediate peritoneal macrophage pyroptosis via NLRP3/caspase-1/GSDMD in mice [ 13 ], contributing to the host resistance to Giardia infection and pathogenesis. Pyroptosis, a controlled cell death that is a component of the host's innate immune responses, is dependent on the creation of plasma membrane holes by proteins from the gasdermin family [ 14 ]. Cell swelling, plasma membrane rupture, chromatin breakage and the release of inner pro-inflammatory substances are its distinguishing features [ 15 , 16 ].…”