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Last update 08 May 2025

CASP5

Last update 08 May 2025

Basic Info

Synonyms

CASP-5, CASP5, caspase 5

+ [10]

Introduction

Thiol protease that acts as a mediator of programmed cell death (PubMed:28314590, PubMed:29898893). Initiates pyroptosis, a programmed lytic cell death pathway through cleavage of Gasdermin-D (GSDMD): cleavage releases the N-terminal gasdermin moiety (Gasdermin-D, N-terminal) that binds to membranes and forms pores, triggering pyroptosis (PubMed:29898893). Also mediates cleavage and maturation of IL18 (PubMed:37993714). Cleavage of GSDMD and IL18 is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 (PubMed:37993714). During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).

Drugs associated with CASP5

Caspase-4/5 inhibitor(Ventus)

Target

CASP4 x CASP5

Mechanism

CASP4 inhibitors [+1]

Active Org.

Ventus Therapeutics, Inc.

Originator Org.

Ventus Therapeutics, Inc.

Active Indication

Inflammation

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CASP5

100 Translational Medicine associated with CASP5

0 Patents (Medical) associated with CASP5

296

Literatures (Medical) associated with CASP5

31 Dec 2025·Virulence

Human macrophage response to the emerging enteric pathogen Aeromonas veronii : Inflammation, apoptosis, and downregulation of histones

Article

Author: Naidovski, Nicholas ; Riordan, Stephen M. ; Chong, Sarah K. T. ; Wehrhahn, Michael C. ; Liu, Fang ; Yuwono, Christopher ; Zhang, Li

This study investigated the pathogenic mechanisms of Aeromonas veronii in macrophages. THP-1 derived macrophages were used as a human macrophage model and were treated with A. veronii strain AS1 isolated from intestinal biopsies of an IBD patient, or Escherichia coli strain K-12. RNA was extracted and subjected to RNA sequencing and comparative transcriptomic analyses. Protein levels of IL-8, IL-1β, IL-18, and TNFα were measured using ELISA, and apoptosis was assessed using caspase 3/7 assays. Both A. veronii AS1 and E. coli K-12 significantly upregulated the expression of many genes involving inflammation. At the protein level, A. veronii AS1 induced significantly higher levels of IL-8, TNFα, mature IL-18 and IL-1β than E. coli K-12, and led to greater elevation of caspase 3/7 activities. Both A. veronii AS1 and E. coli K-12 upregulated the expression of CASP5, but not other caspase genes. A. veronii AS1 significantly downregulated the expression of 20 genes encoding histone proteins that E. coli K-12 did not. The more profound pathogenic effects of A. veronii in inducing inflammation and apoptosis in macrophages than E. coli K-12 are consistent with its role as a human enteric pathogen. The upregulated expression of CASP5 and increased release of IL-1β and IL-18 support the role of CASP5 in activation of non-canonical inflammasome. The downregulation of histone genes by A. veronii suggests a unique impact on host cell gene expression, which may represent a novel virulence strategy. These findings advance the understanding of pathogenic mechanisms of the emerging human enteric pathogen A. veronii.

01 May 2025·Brain Research

Comprehensive analysis of the role of Caspases in glioma

Article

Author: Mei, Qunfang ; Mei, Pengying ; Wang, Heming

Caspases (CASPs) are attractive targets for cancer therapy. Many prognostic models based on gene signatures include genes from the CASPs family in diffuse glioma. CASP3, CASP4 and CASP6 in glioma have been studied individually. However, specialized comprehensive analysis of the roles of CASPs family in glioma is lacking. Therefore, this study utilized bioinformatics methods to investigate this issue. CASP1-10 expressionlevels were significantly up-regulated in LGG and GBM and glioma, and varied significantly across different clinical subgroups of glioma and LGG and various cell types, and most of CASP1-10 members showed significant differences in recurrence status of LGG. 10 signatures (CASP1-10) were associated with poor overall survival (OS) in glioma and LGG and GBM. However, pan-cancer survival analysis showed that CASP1-10 were associated with the prognosis of LGG, but not GBM. CASP1-10 were related to poor prognosis of glioma and LGG, except for CASP9, which was the opposite of a protective factor. CASP1-10 were independent prognostic factors for OS in glioma and LGG, except for CASP5, and also for recurrence-free survival (RFS) in LGG. Most of CASP1-10 were also independent prognostic factors for disease-specific survival (DSS) and progression-free interval (PFI) and had diagnostic value in glioma and LGG. Genetic alterations of CASP1-10 genes set were associated with poor prognosis in LGG. CASP1-10 were involved in immune infiltration and programmed cell death in glioma and LGG and GBM, and might promote the apoptosis of immune cells. Compared to GBM, CASP1-10 had a more significant impact on the prognosis, cancer-related pathways, and immune infiltration in LGG, indicating that CASP1-10 might play important roles in the recurrence and progression of LGG, and might be promising therapeutic targets for LGG. Therefore, it is speculated that natural caspase inhibitor p35 may be a promising drug for the treatment of glioma, especially for LGG.

01 Feb 2025·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

Overexpression of inflammatory human caspase-4 in relation to clinical severity of oral lichen planus

Article

Author: Krisanaprakornkit, Warisara ; Makeudom, Anupong ; Tangjarroenphakdee, Chavanya ; Tipsirisakun, Panatda ; Krisanaprakornkit, Suttichai ; Jeerachaipansakul, Anupong ; Hengsanankul, Nattapat ; Maneerat, Darussakorn ; Atijit, Chanipa

OBJECTIVEInvolvement of non-canonical inflammasome, comprising inflammatory human caspase-4, caspase-5, and Gasdermin D, in the pathogenesis of oral lichen planus (OLP) has never been demonstrated. We aimed to determine human caspase-4, caspase-5, and Gasdermin D expressions in OLP, to correlate their expressions with OLP severity, and to measure salivary interleukin (IL)-1β levels.STUDY DESIGNOLP and normal oral mucosal specimens (n = 42 each) were processed for immunohistochemistry or immunoblotting. The clinical score for OLP severity was assessed at the most severe site. The immunohistochemical (IHC) score was a summation of intensity and positive cell scores. Salivary IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA).RESULTSMedian IHC scores of caspase-4 and Gasdermin D in OLP group were significantly greater than those in normal mucosal group (P < .01), consistent with significantly upregulated expressions by immunoblotting (P < .05). The IHC scores of caspase-4 and Gasdermin D were positively correlated with the clinical scores (P < .05). Salivary IL-1β levels in the OLP group were significantly greater than those in the normal mucosal group (P < .001).CONCLUSIONSOur study demonstrates enhanced human caspase-4 and Gasdermin D expressions in relation to increased OLP severity with elevated salivary IL-1β levels, proposing clinical applications of these biomolecules as potential prognostic markers and/or new therapeutic intervention for OLP.

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