Ask about this productRelated genes to: CTSS Blocking Peptide
- Gene:
- CTSS NIH gene
- Name:
- cathepsin S
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 1q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 1992-07-09
- Date modifiied:
- 2016-10-05
Related products to: CTSS Blocking Peptide
Related articles to: CTSS Blocking Peptide
- Disease-modifying therapies for Alzheimer's disease (AD) targeting amyloid-β and tau have consistently failed, highlighting the urgent need for innovative therapeutic strategies. Cathepsin S (CTSS), a lysosomal cysteine protease upregulated in AD, functions as a "multifaceted disruptor" that interconnects neuroinflammation, blood-brain barrier (BBB) dysfunction, and Aβ metabolic dysregulation. Although exercise is a validated non-pharmacological intervention that mitigates AD pathology, its multi-target molecular mechanisms remain elusive. Here, we propose and substantiate the "Exercise-CTSS-AD Axis" hypothesis, positing that exercise confers neuroprotection by suppressing CTSS through synergistic anti-inflammatory, anti-aging, and metabolic regulatory pathways. Exercise-induced myokines and clearance of senescent cells inhibit CTSS transcription, while AMPK-TFEB axis activation enhances lysosomal function to repress CTSS enzymatic activity. This systemic CTSS suppression preserves BBB integrity, ameliorates microglia-driven neuroinflammation, and restores Aβ homeostasis by reducing production and enhancing clearance. Our framework provides a unifying molecular explanation for the pleiotropic benefits of exercise, positions CTSS as a quantifiable biomarker for personalized exercise regimens, and supports an innovative combinatorial strategy: "Exercise + low-dose CTSS inhibitors" as a disease-modifying therapy for AD. - Source: PubMed
Publication date: 2026/07/17
Yang DongGuo WenWang Bihan - Plasticizer exposure has been associated with gestational diabetes mellitus (GDM), but the placental toxicogenomic mechanisms that may connect environmental chemical signals to maternal dysglycaemia remain unresolved. We integrated plastic-associated compound target annotation, placental bulk transcriptomics, cis-eQTL-based Mendelian randomization (MR), Bayesian colocalization, machine-learning prioritization, pathway analysis, placental single-cell transcriptomics and trophoblast validation. Candidate targets were intersected with GDM-related placental expression signals and tested against FinnGen GDM summary statistics using blood-derived cis-eQTL instruments. Among expression-supported targets, 15 genes showed nominal MR associations with GDM and 11 loci showed colocalization support. LASSO regression and random forest prioritization converged on AKT1, CLEC7A and CTSS. Expression-direction checks showed concordance between bulk placental expression and MR direction for AKT1 and CTSS, whereas CLEC7A showed a discordant genetic direction and was therefore interpreted cautiously. Functional analyses placed these genes in immune, redox and metabolic pathways, while single-cell data localized them to trophoblast and immune-related placental compartments. In HTR-8/SVneo trophoblast cells, di-(2-ethylhexyl) phthalate (DEHP) exposure altered CLEC7A expression, providing targeted evidence that CLEC7A is phthalate-responsive at the mRNA level under the tested conditions. The two-dose design did not support a formal concentration-response conclusion. The findings define a toxicogenomic hypothesis in which plasticizer-related stress intersects with placental immunometabolic regulation in GDM. The study does not establish direct exposure causality, but it prioritizes testable placental targets for exposure-resolved toxicological and epidemiological validation. - Source: PubMed
Publication date: 2026/07/08
Wen XiaotingLu HainiaoZhou YingziHuang MinXiao Yunzhou - Tubulointerstitial fibrosis (TIF) plays an important role in the deterioration of diabetic kidney disease (DKD). Epithelial-to-mesenchymal transition (EMT) in tubular epithelial cells (TECs) leads to TIF in the progression of DKD. Hypoxia-inducible factor-1α (HIF-1α; HIF1A) has been elucidated to promote EMT and TIF through inducing transforming growth factor-β1 (TGF-β1) pathway. In this study, we aimed to explore the mediation effect of key genes in HIF‑1α‑induced EMT and TIF in DKD. Tubulointerstitial gene expression profiling data from DKD patients and healthy controls (HCs) were acquired from the GEO database, R packages were used for bioinformatics analysis, and the db/db mice and proximal TEC line (HK-2) were used to validate the bioinformatic findings. Consequently, we focused on cathepsin S (CTSS). Functional enrichment indicated that HIF1A and CTSS were jointly involved in inflammatory activation, extracellular matrix deposition, and cellular interaction. and experiments validated that in DKD models, HIF‑1α could upregulate Cathepsin S to promote partial EMT-associated phenotypic shift and fibrotic remodeling in TECs, thereby deteriorating diabetic kidney injury. Conclusively, CTSS may serve as a downstream effector of HIF‑1α participating in the regulation of partial EMT-associated phenotypic shift and fibrotic remodeling of TECs in diabetic kidney disease models. - Source: PubMed
Publication date: 2026/07/01
Zhang HaidongLi QiWang YueQiong Bai - Cysteine cathepsins, particularly cathepsin S, regulate proteolytic signaling in cancer progression and immune modulation, yet selective tools for individual cathepsins remain limited. Here, we report the design of cathepsin S-selective probes and cathepsin S-cleavable antibody-drug conjugates (ADCs) using substrate profiling with unnatural amino acids. Hybrid Combinatorial Substrate Library (HyCoSuL) screening identified selective tetrapeptide motifs that were used to develop optimized fluorogenic substrates, irreversible inhibitors, and fluorescent activity-based probes with high selectivity for cathepsin S in biochemical and cellular assays. These peptide motifs were then incorporated as cleavable linkers in MMAE-based ADCs targeting HER-2 or TROP-2, enabling cathepsin S-dependent cytotoxicity across breast cancer models with distinct target-expression profiles. Finally, anti-cathepsin S antibodies combined with CyTOF analysis revealed the spatial distribution of cathepsin S and its coexpression with HER-2 and TROP-2 in breast cancer patient samples, suggesting that cathepsin S profiling may help inform future patient stratification strategies for cathepsin S-activated ADC therapy. - Source: PubMed
Publication date: 2026/06/30
Łęcka MariaGorzeń OliwiaĆwilichowska-Puślecka NataliaNguyen JuliaMajchrzak MartynaPippa VanessaJakimowicz PiotrWiśniewski JerzyDołęga-Kozierowski BartoszKasprzak PiotrTurk BorisDrąg MarcinMatkowski RafałPoręba Marcin - Intracerebral hemorrhage (ICH) causes secondary white matter injury, which contributes substantially to long-term neurological disability. Although macrophages accumulate in the perihematomal region and participate in tissue remodeling after ICH, the molecular programs that link macrophage responses to white matter repair remain poorly understood, and no current strategies specifically target macrophage‑mediated white matter restoration. Cathepsin S (CTSS), a lysosomal cysteine protease involved in immune regulation and tissue remodeling, is strongly induced after brain injury; however, its role in post‑ICH white matter pathology has not been defined. - Source: PubMed
Publication date: 2026/06/30
Yu XianHuang HuapingMao DandanWu JiananPan JiaheKuang YiruiWu YiwenChen HuaijunFan LinfengZheng YongheZhou JiayinJiang ShandongWu XinyanZhou HangYan WeiZheng HaiyanChen JingyinChen GaoGu Chi