NLRP1 Inflammasomes: A Potential Target for the Treatment of Several Types of Brain Injury

Abstract

NOD-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) is a member of the NLR family. The NLRP1 inflammasome consists of the NLRP1 protein, the adaptor protein apoptosis-associated speck-like protein containing a CARD domain, and the effector molecule pro-caspase-1. When stimulated, the inflammasome initiates the cleavage of pro-caspase-1 and converts it into its active form, caspase-1; then, caspase-1 facilitates the cleavage of the proinflammatory cytokines interleukin-1β and interleukin-18 into their active and secreted forms. In addition, caspase-1 also mediates the cleavage of gasdermin D, which leads to pyroptosis, an inflammatory form of cell death. Pathological events that damage the brain and result in neuropathological conditions can generally be described as brain injury. Neuroinflammation, especially that driven by NLRP1, plays a considerable role in the pathophysiology of brain injury, such as early brain injury (EBI) of subarachnoid hemorrhage, ischemic brain injury during stroke, and traumatic brain injury (TBI). In this article, a thorough overview of NLRP1 is presented, including its structure, mechanism of activation, and role in neuroinflammation. We also present recent studies on NLRP1 as a target for the treatment of EBI, ischemic brain injury, TBI, and other types of brain injury, thus highlighting the perspective of NLRP1 as an effective mediator of catastrophic brain injury.

Inflammasome activation in response to aberrations of cellular homeostasis in epithelial cells from human cornea and retina

“…Recently, it has been shown that NLRP1 is the predominant inflammasome in UVB‐irradiated primary human skin keratinocytes (Burian & Yazdi, 2018; Fenini et al., 2018; Lee et al., 2022). Similar to NLRP3, the NLRP1 inflammasome requires caspase‐1 to convert pro‐IL‐1β and pro‐IL‐18 into its active form (Mi et al., 2022). Additionally, NLRP1 is known to be secreted out of the cell after the activation of the inflammasome (Feldmeyer et al., 2007), which is comparable to the disposal of NLRP3 (Baroja‐Mazo et al., 2014; Piippo, Korhonen, Hytti, Skottman, et al., 2018).…”

Recent advances in pyroptosis, liver disease, and traditional Chinese medicine: A review

“…PRRs are germline‐encoded receptors that can directly recognize specific proteins on the surface of pathogenic microorganisms, senescent cells, or apoptotic cells. The toll‐like receptors (TLRs) and NOD‐like receptors are the typical examples of PRRs (Mi et al, 2022). PRRs recognize PAMP and DAMP unique recognition targets: C‐terminal domains, leucine‐rich repeats (LRRs), C‐type lectin‐like domain, and DNA‐ or RNA‐binding structural domains.…”

“…The structure of human NLRP1 is represented by an N‐terminal PYD, NACHT (NAIP, CIITA, HET‐E, and TP‐1) domain, LRR domain, function‐to‐find domain (FIIND) comprising ZU5 and UPA domains, and CARD domain at the C‐terminus (Figure 2). Unlike other members of the NOD‐like receptor family, human NLRP1 contains 1473 amino acids with a molecular weight of 165.9 kDa (Kersse et al, 2011; Mi et al, 2022). Upon stimulation, the FIIND of NLRP1 undergoes its own protein hydrolysis to produce the FIIND UPA ‐CARD fragment (Gong et al, 2021; Sandstrom et al, 2019).…”

“…The mechanisms by which NLRP3-mediated pyroptosis regulates the progression of liver diseases are listed in Table 1. molecular weight of 165.9 kDa (Kersse et al, 2011;Mi et al, 2022).…”

Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries

“…The oligomers of PFD bind to the cell membrane and form macropores on the membrane, resulting in cell swelling and membrane rupture ( Al Mamun et al, 2022 ). Increasing evidence indicates that pyroptosis is involved in many diseases, including CNS injuries ( Mi et al, 2022 ; Wu et al, 2022 ).…”