ArticleJournal of neuroinflammation2017
A role for cathepsin Z in neuroinflammation provides mechanistic support for an epigenetic risk factor in multiple sclerosis.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 62 citations in OpenAlex.
- Circulating neuronal proteins are elevated in severe autism and associated with patient-specific neuronal dysfunction and behavioral deficits.Translational psychiatry · 2026Article
- Glial Cysteine Cathepsins: From Homeostasis to Neurodegeneration.Cellular and molecular neurobiology · 2026Review
- Cathepsin Z/X: Breaking Down the Known and Unknown.International journal of molecular sciences · 2026Review
- Computational identification of migrating T cells in spatial transcriptomics data.JCI insight · 2026Article
- Targeting Cathepsin Z suppresses endometriosis via the AMPK/mTOR-mediated autophagy and apoptosis axis.Frontiers in medicine · 2026Article
- Targeting Cathepsins in Neurodegeneration: Biochemical Advances.Biomedicines · 2025Review
- Proteomic Analysis of Mouse Cerebral Cortex Following Experimental Ischemic Stroke: Identifying Novel Biomarkers of Damage and Repair.Cellular and molecular neurobiology · 2025Article
- Review
- Cathepsin Z is a conserved susceptibility factor underlying tuberculosis severity.PLoS biology · 2025Article
- Cathepsins in Neurological Diseases.International journal of molecular sciences · 2025Review
- Lysosome-related proteins may have changes in the urinary exosomes of patients with acute gout attack.European journal of medical research · 2025Article
- Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis.Frontiers in immunology · 2025Article
- Unveiling the Role of Cathepsins on Lung Function in Chronic Obstructive Pulmonary Disease: A Mendelian Randomization Analysis.International journal of chronic obstructive pulmonary disease · 2025Article
- Granulins rescue inflammation, lysosome dysfunction, lipofuscin, and neuropathology in a mouse model of progranulin deficiency.Cell reports · 2024Article
- BTK regulates microglial function and neuroinflammation in human stem cell models and mouse models of multiple sclerosis.Nature communications · 2024Article
- Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Cathepsin X deficiency alters the processing and localisation of cathepsin L and impairs cleavage of a nuclear cathepsin L substrate.Biological chemistry · 2024Article
- Fluorofenidone attenuates renal fibrosis by inhibiting lysosomal cathepsin‑mediated NLRP3 inflammasome activation.Experimental and therapeutic medicine · 2024Article
- The Role of Cysteine Protease Cathepsins B, H, C, and X/Z in Neurodegenerative Diseases and Cancer.International journal of molecular sciences · 2023Review
- V-Set Immunoglobulin Domain-Containing Protein 4 as a Novel Serum Biomarker of Lupus Nephritis and Renal Pathology Activity.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundHypomethylation of the cathepsin Z locus has been proposed as an epigenetic risk factor for multiple sclerosis (MS). Cathepsin Z is a unique lysosomal cysteine cathepsin expressed primarily by antigen presenting cells. While cathepsin Z expression has been associated with neuroinflammatory disorders, a role for cathepsin Z in mediating neuroinflammation has not been previously established.
methodsExperimental autoimmune encephalomyelitis (EAE) was induced in both wildtype mice and mice deficient in cathepsin Z. The effects of cathepsin Z-deficiency on the processing and presentation of the autoantigen myelin oligodendrocyte glycoprotein, and on the production of IL-1β and IL-18 were determined in vitro from cells derived from wildtype and cathepsin Z-deficient mice. The effects of cathepsin Z-deficiency on CD4+ T cell activation, migration, and infiltration to the CNS were determined in vivo. Statistical analyses of parametric data were performed by one-way ANOVA followed by Tukey post-hoc tests, or by an unpaired Student's t test. EAE clinical scoring was analyzed using the Mann-Whitney U test.
resultsWe showed that mice deficient in cathepsin Z have reduced neuroinflammation and dramatically lowered circulating levels of IL-1β during EAE. Deficiency in cathepsin Z did not impact either the processing or the presentation of MOG, or MOG- specific CD4+ T cell activation and trafficking. Consistently, we found that cathepsin Z-deficiency reduced the efficiency of antigen presenting cells to secrete IL-1β, which in turn reduced the ability of mice to generate Th17 responses-critical steps in the pathogenesis of EAE and MS.
conclusionTogether, these data support a novel role for cathepsin Z in the propagation of IL-1β-driven neuroinflammation.
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