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Understanding of the pathophysiology of sepsis allows the development of new therapeutic approaches, beyond supportive care and antimicrobial therapy, to help reduce the high mortality rates in intensive care units. In this context, a large number of experimental and clinical studies in the last 20 years support the key role of the endothelium in sepsis in relation to organ failure. This review aims to provide a comprehensive overview of the role of zinc-dependent endopeptidases and their endogenous inhibitors in endothelial dysfunction associated with sepsis as well as in other pathologies. Finally, we discuss that inhibitors of this family of proteases could represent a promising therapeutic approach against sepsis.
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http://dx.doi.org/10.1007/s00011-025-02056-x | DOI Listing |
J Neurochem
August 2025
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, exert their potent neuroparalytic effects by specifically targeting presynaptic cholinergic nerve terminals. BoNTs consist of a heavy chain that mediates high-affinity neuronal binding and endocytosis, and a light chain that, once translocated into the cytosol, acts as a zinc-dependent metalloprotease. The light chain cleaves SNARE proteins essential for synaptic vesicle fusion, thereby inhibiting acetylcholine release and leading to flaccid paralysis.
View Article and Find Full Text PDFInt J Mol Sci
July 2025
Oncology Research Laboratory, Institute of Oncology, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania.
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders characterized by excessive proliferation of one or more myeloid lineages, frequently accompanied by an elevated risk of thrombotic events. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are implicated in numerous inflammatory and vascular pathophysiological processes. In this study, we analyzed the association between selected polymorphisms, rs1799750, rs243865, rs3025058, rs3918242, and rs17576, and thrombotic risk as well as clinical characteristics in patients with MPNs.
View Article and Find Full Text PDFInflamm Res
June 2025
Biocritic, Group for Biomedical Research in Critical Care Medicine, 47005, Valladolid, Spain.
Understanding of the pathophysiology of sepsis allows the development of new therapeutic approaches, beyond supportive care and antimicrobial therapy, to help reduce the high mortality rates in intensive care units. In this context, a large number of experimental and clinical studies in the last 20 years support the key role of the endothelium in sepsis in relation to organ failure. This review aims to provide a comprehensive overview of the role of zinc-dependent endopeptidases and their endogenous inhibitors in endothelial dysfunction associated with sepsis as well as in other pathologies.
View Article and Find Full Text PDFToxins (Basel)
June 2025
Department of Biomedical Sciences, Division of Microbiology and Virology, University of Sassari, 07100 Sassari, Italy.
Enterotoxigenic (ETBF) has emerged as a gut microbiome pathogen that can promote intestinal inflammation and contribute to colorectal cancer (CRC). Its principal virulence factor, the toxin (BFT), is a zinc-dependent metalloprotease that disrupts epithelial barrier integrity, initiates inflammatory signaling pathways, and enhances epithelial proliferation. Although growing evidence supports a link between ETBF and CRC, some inconsistencies across studies highlight the need for further investigation into the molecular mechanisms underpinning BFT-mediated pathogenesis.
View Article and Find Full Text PDFSpectrochim Acta A Mol Biomol Spectrosc
November 2025
Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667 Uttarakhand, India; Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee 247667 Uttarakhand, India. Electronic address:
Inorganic cofactors, such as zinc, contribute to enzymatic reactions, protein folding, and enzyme stability. T7 endolysin or T7 lysozyme (T7L), a zinc-dependent amidase involved in the lysis of bacterial cell walls, has great potential for applications in biotechnology and medicine. The present study provides an in-depth analysis of the structure stability and catalytic features of T7L, focusing on the comparison of its Apo and Holo forms using turbidimetric assay, circular dichroism, fluorescence spectroscopy, nuclear magnetic resonance (NMR) spectroscopic methods and molecular dynamics simulations.
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