ArticleCell death & disease2023
Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Genetic overlap and causality between depression and preterm birth: a large-scale genome-wide cross-trait analysis.Psychological medicine · 2025Pooled it
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- METTL3-dependent m⁶A maturation of miR-140-3p contributes to hippocampal neuronal apoptosis through the OTX2/Wnt/β-catenin axis under chronic stress.Molecular biology reports · 2026Article
- Curcumin alleviates depression-aggravated psoriasis by targeting MMP9-regulated apoptotic pathways.iScience · 2026Article
- Review
- NLRP6 governs hippocampal microglial phagocytosis to resist stress-induced depressive-like behaviors in mice and the intervention effect of bezafibrate.Journal of advanced research · 2026Article
- Abnormal iron homeostasis mediates cochlear hair cell impairment and hearing loss in Gprasp2-deficient mice.Communications biology · 2026Article
- Outer membrane vesicles fromFrontiers in microbiology · 2026Article
- Pharmacological mechanisms of natural products with antidepressant effects: A focus on the programmed cell death regulation.Journal of pharmaceutical analysis · 2026Review
- Follicular fluid proteomic alterations associated with oocyte developmental potential in polycystic ovary syndrome.Frontiers in endocrinology · 2026Article
- Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025Review
- [Helicid alleviates depression-like behavior in rats with chronic unpredictable mild stress through the NCALD/sGC/cGMP/PKG axis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Geniposide attenuates astrocyte pyroptosis in depression via long non-coding RNA Six3os1-mediated regulation of the miR-511-3p/COL9A3 axis and MAPK/NLRP3 signaling.Journal of cell communication and signaling · 2025Article
- Norepinephrine Induces Sertoli Cell Ferroptosis via Receptors Desensitization Causing Stress-Related Male Reproductive Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A classic traditional chinese medicine formula for depression: mechanistic insights from phytochemical constituents and multitarget pathways.Psychopharmacology · 2025Article
- Ginkgo biloba L. leaf extract (EGb 761) alleviates reserpine-induced depression-like symptoms in aged rats by enhancing serotonin/norepinephrine levels and reducing oxidative/nitrosative stress.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- KLK8: charting new territories in left ventricular hypertrophy biomarker research.Biomarkers in medicine · 2025Article
- Biological mechanism and functional verification of key genes related to major depressive disorder and type 2 diabetes mellitus.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- KLK8/HGF/Met signaling pathway mediates diabetes-associated hippocampal neuroinflammation in male mice.Theranostics · 2025Article
- Oxysophocarpine Prevents the Glutamate-Induced Apoptosis of HT-22 Cells via the Nrf2/HO-1 Signaling Pathway.Current issues in molecular biology · 2024Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal apoptosis has been well-recognized as a critical mediator in the pathogenesis of depressive disorders. Tissue kallikrein-related peptidase 8 (KLK8), a trypsin-like serine protease, has been implicated in the pathogenesis of several psychiatric disorders. The present study aimed to explore the potential function of KLK8 in hippocampal neuronal cell apoptosis associated with depressive disorders in rodent models of chronic unpredictable mild stress (CUMS)-induced depression. It was found that depression-like behavior in CUMS-induced mice was associated with hippocampal KLK8 upregulation. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency attenuated CUMS-induced depression-like behaviors and hippocampal neuronal apoptosis. In HT22 murine hippocampal neuronal cells and primary hippocampal neurons, adenovirus-mediated overexpression of KLK8 (Ad-KLK8) was sufficient to induce neuron apoptosis. Mechanistically, it was identified that the neural cell adhesion molecule 1 (NCAM1) may associate with KLK8 in hippocampal neurons as KLK8 proteolytically cleaved the NCAM1 extracellular domain. Immunofluorescent staining exhibited decreased NCAM1 in hippocampal sections obtained from mice or rats exposed to CUMS. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency largely prevented CUMS-induced loss of NCAM1 in the hippocampus. Both adenovirus-mediated overexpression of NCAM1 and NCAM1 mimetic peptide rescued KLK8-overexpressed neuron cells from apoptosis. Collectively, this study identified a new pro-apoptotic mechanism in the hippocampus during the pathogenesis of CUMS-induced depression via the upregulation of KLK8, and raised the possibility of KLK8 as a potential therapeutic target for depression.
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