Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(4)

Published: April 8, 2023

Cathepsin B (CatB), a cysteine protease, is primarily localized within subcellular endosomal and lysosomal compartments. It involved in the turnover of intracellular extracellular proteins. Interest growing CatB due to its diverse roles physiological pathological processes. In functional defective tissues, programmed cell death (PCD) one regulable fundamental mechanisms mediated by CatB, including apoptosis, pyroptosis, ferroptosis, necroptosis, autophagic death. However, CatB-mediated PCD responsible for disease progression under conditions. this review, we provide an overview critical regulatory pathways different types PCD, discuss possibility as attractive target multiple diseases. We also summarize current gaps understanding involvement highlight future avenues research.

Language: Английский

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Cathepsin B in cardiovascular disease: Underlying mechanisms and therapeutic strategies

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(17)

Published: Sept. 1, 2024

Abstract Cathepsin B (CTSB) is a member of the cysteine protease family, primarily responsible for degrading unnecessary organelles and proteins within acidic milieu lysosomes to facilitate recycling. Recent research has revealed that CTSB plays multifaceted role beyond its function as proteolytic enzyme in lysosomes. Importantly, recent data suggest significant impacts on different cardiac pathological conditions, such atherosclerosis (AS), myocardial infarction, hypertension, heart failure cardiomyopathy. Especially context AS, preclinical models clinical sample imaging indicate cathepsin activity‐based probe can reliably image activity foam cells atherosclerotic plaques; concurrently, it allows synchronous diagnostic therapeutic interventions. However, our knowledge cardiovascular disease still early stage. This paper aims provide comprehensive review significance physiology pathology, with objective laying theoretical groundwork development drugs targeting CTSB.

Language: Английский

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Smart Delivery Systems Responsive to Cathepsin B Activity for Cancer Treatment

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(7), P. 1848 - 1848

Published: June 29, 2023

Cathepsin B is a lysosomal cysteine protease, contributing to vital cellular homeostatic processes including protein turnover, macroautophagy of damaged organelles, antigen presentation, and in the extracellular space, it takes part tissue remodeling, prohormone processing, activation. However, aberrant overexpression cathepsin its enzymatic activity associated with different pathological conditions, cancer. tumor tissues makes this enzyme an important target for smart delivery systems, responsive enzyme. The generation technologies which therapeutic effect activated as result cleavage provides opportunity tumor-targeted therapy controlled drug release. In review, we summarized designed improve current cancer treatments that were shown play key role disease progression response treatment.

Language: Английский

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The causal relationship between cathepsins and digestive system tumors: a Mendelian randomization study

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: March 25, 2024

Background Multiple studies have confirmed the significant role of cathepsins in development and progression digestive system tumors. However, further investigation is needed to determine causal relationships. Methods We conducted a two-sample bidirectional Mendelian randomization (MR) study using pooled data from genome-wide association (GWAS) assess associations between nine (cathepsin B, E, F, G, H, L2, O, S, Z) six types tumors, including hepatocellular carcinoma (HCC), pancreatic cancer (PCa), biliary tract (BTC), colorectal (CRC), gastric (GC), esophageal (EC). employed following methods inverse variance weighting (IVW), MR-Egger, weighted median (WM), Cochran’s Q, MR-PRESSO, MR-Egger intercept test leave-one-out sensitivity analysis. The STROBE-MR checklist for reporting MR was used this study. Results risk HCC increased with high levels cathepsin G (IVW: p = 0.029, odds ratio (OR) 1.369, 95% confidence interval (CI) 1.033-1.814). Similarly, BTC associated elevated B 0.025, OR 1.693, CI 1.070-2.681). Conversely, reduction PCa H 0.027, 0.896, 0.812-0.988). Lastly, L2 were found lower CRC 0.034, 0.814, 0.674-0.985). Conclusion Our findings confirm relationship which can offer valuable insights diagnosis treatment

Language: Английский

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Cathepsin B induces kidney diseases through different types of programmed cell death

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 10, 2025

Cathepsin B (CTSB), a key cysteine protease, plays essential roles in physiological and pathological processes. As research progresses, interest how CTSB triggers different types of programmed cell death (PCD) to induce the onset development diseases is increasing. Several recent studies suggest that PCD mediated by play kidney diseases. In this review, we outline fundamental mechanisms which several discuss function various segments kidney. Moreover, explore possibilities prospects using as therapeutic target for

Language: Английский

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Identification of functional biomarkers for personalized nanomedicine in advanced breast cancer in vitro models

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113584 - 113584

Published: March 1, 2025

Language: Английский

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Interleukin-6/soluble IL-6 receptor-induced secretion of cathepsin B and L from human gingival fibroblasts is regulated by caveolin-1 and ERK1/2 pathways

Frontiers in Dental Medicine, Journal Year: 2025, Volume and Issue: 6

Published: March 11, 2025

Aims Cathepsins are essential lysosomal enzymes that maintain organismal homeostasis by degrading extracellular substrates. The inflammatory cytokine interleukin-6 (IL-6) increases the production of cathepsins through caveolin-1 (Cav-1) and c-Jun N-terminal kinase (JNK) signaling pathways, which have been implicated in destruction periodontal tissue. This study investigated effect IL-6/soluble IL-6 receptor (sIL-6R) complex on secretion human gingival fibroblasts (HGFs) examined function extracellularly secreted B L under acidic culture conditions vitro . Methods HGFs were isolated from healthy volunteer donors. expression Cav-1 was suppressed via transfection with small interfering RNA (siRNA) targeting Cav-1. levels induced IL-6/sIL-6R measured using western blotting enzyme-linked immunosorbent assay. Extracellular cathepsin activity following stimulation assessed a methylcoumarylamide substrate fluorescence-based IL-6/sIL-6R-induced quantified inhibitory for signal-regulated (ERK) 1/2 and/or JNK signaling, both transduction pathways activated IL-6/sIL-6R. quantification also performed blotting. Results their precursor forms HGFs, significantly elevated protein observed at 24, 48, 72 h post-IL-6/sIL-6R stimulation. Under conditions, increased 48 h. suppression inhibited regardless stimulation, whereas reduced only after Inhibition ERK1/2 decreased inhibition similar conditions. Conclusion precursors these became involved regulating precursors.

Language: Английский

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Cathepsins and their role in gynecological cancers: Evidence from two-sample Mendelian randomization analysis

Medicine, Journal Year: 2025, Volume and Issue: 104(10), P. e41653 - e41653

Published: March 7, 2025

Prior studies have reported connections between cathepsins (CTS) and gynecological cancers; however, the exact causal links are yet to be fully understood. Leveraging publicly accessible genome-wide association study summary datasets, we performed a two-sample bidirectional Mendelian randomization (MR) multivariate MR (MVMR) analysis, with inverse variance weighted (IVW) method as primary approach. analysis demonstrated associations CTSB cervical cancer (IVW: odds ratio [OR] = 0.9995, 95% confidence interval [CI] 0.9991-0.9999, P .0418), CTSE ovarian OR 0.9197, CI 0.8505-0.9944, .0358), CTSZ 0.9449, 0.8938-0.9990, .0459), high grade serous 0.8939, 0.8248-0.9689, .0063), 0.9269, 0.8667-0.9913, .0268). A positive correlation was identified CTSH clear cell 1.1496, 1.0368-1.2745, .0081). Nevertheless, subsequent adjustment for false discovery rate revealed that none of P-values retained statistical significance (PFDR > 0.05). MVMR results elucidated inversely associated 0.9988, 0.9981-0.9996, .0022). Moreover, noted CTSF 1.0007, 1.0000-1.0014, .0364), similarly, CTSS 1.0005, 1.0000-1.0011, .0490). CTSO exhibited non-endometrioid endometrial 1.4405, 1.1864-1.7490, < .001), positively 1.1167, 1.0131-1.2310, .0263). The findings reveal emerges protective element against cancer, whereas represent risk factors this disease. stands out factor acts cancer. This elucidates causative CTS cancers, providing innovative insights diagnostic therapeutic optimization.

Language: Английский

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Structure-guided virtual screening reveals phytoconstituents as potent cathepsin B inhibitors: Implications for cancer, traumatic brain injury, and Alzheimer’s disease

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: April 16, 2025

Cathepsin B (CathB) is a lysosomal cysteine protease involved in various pathological and physiological processes becoming an attractive target for drug intervention complex diseases like cancer, traumatic brain injury (TBI) Alzheimer's disease (AD). The aberrant expression of CathB drives tumor invasiveness metastasis exacerbates neurodegeneration behavioral deficits AD TBI. However, current inhibitors lack clinical translation due to poor selectivity, bioavailability, or toxicity, necessitating novel therapeutic candidates. To address this gap, silico screening was conducted through the structure-guided virtual with IMPPAT 2 phytochemical library potential inhibitors. Using control inhibitor CA-074Me as benchmark, two phytoconstituents, Nicandrenone Picrasidine M, emerged superior binding affinities, ligand efficiency, robust interactions active site residues CathB. These molecules were further validated molecular dynamics (MD) simulations, which supported their ability bind stably pocket thus likely hold durable inhibitory activity. Remarkably, these phytoconstituents exhibited favorable pharmacokinetic ADMET profiles, validate lead compounds. study showed that bioactive compounds could be developed new inhibitors, opening frontier use management such TBI, AD.

Language: Английский

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Cathepsin B-Activated PET Tracer for In Vivo Tumor Imaging

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 21(3), P. 1382 - 1389

Published: Feb. 19, 2024

Cathepsin B, a lysosomal protease, is considered as crucial biomarker for tumor diagnosis and treatment it overexpressed in numerous cancers. A stimulus-responsive SF scaffold has been reported to detect the activity of variety tumor-associated enzymes. In this work, small-molecule PET tracer ([68Ga]NOTA-SF-CV) was developed by combining an with cathepsin B-specific recognition substrate Cit-Val. Upon activation [68Ga]NOTA-SF-CV could form cyclization product reduction environment, resulting reduced hydrophilicity. This unique property effectively prevent exocytosis B-overexpressing cells, leading prolonged retention amplified imaging signal. Moreover, had great targeting specificity B. vivo microPET results showed that able visualize expression level B various tumors. Hence, may be served potential diagnosing B-related diseases.

Language: Английский

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