{
  "abstract": "Meprin β is a zinc-dependent metalloprotease of the astacin family highly expressed in kidney and intestine. Dysregulation of meprin β expression and activity was observed in several pathological conditions such as Alzheimer’s disease, cancer, fibrosis, and inflammatory bowel disease. Therefore, inhibition of meprin β could be a promising therapeutic option to treat pathological conditions influenced by this protease. However, available small-molecule compounds such as the broad-spectrum metalloproteinases inhibitors marimastat or actinonin lack specificity. Hence, more selective meprin β inhibitors needs to be developed. Here, we provide evidence that the synthetically generated cognate meprin β propeptide serves as highly specific inhibitor for the protease (IC 50 = 1.35 µM), while other related metalloproteases such as meprin α and a disintegrin and metalloproteinases (ADAMs) are not affected. Employing a targeted approach revealed that removal of the last four C-terminal amino acids of the propeptide significantly improved its inhibitory capacity (IC 50 = 0.68 µM). In cell-based experiments, treatment with the propeptide resulted in diminished meprin β activity and decreased cleavage of its substrates, including the interleukin-6 receptor (IL-6R) and the G protein-coupled receptor latrophilin-3 (LPHN3). Suitability was further confirmed in ex vivo cultivated organotypic brain slices, where the administration of the propeptide also resulted in decreased meprin β activity and diminished latrophilin-3 cleavage. Thus, not only the synthetic wildtype propeptide but especially a C-terminally truncated propeptide of meprin β represent highly specific inhibitors with potential for therapeutic application.",
  "abstract_shown": true,
  "affiliations": [
    "Biochemical Institute, Unit for Degradomics of the Protease Web, Kiel University, Otto-Hahn-Platz 9, Kiel, 24118, Germany.",
    "Dept. of Immunology and Regenerative Biology, Weizmann Institute of Science, Max and Lillian Candiotty Building, Room 207, 234 Herzl St. Rehovot, Rehovot, 76100, Israel.",
    "Department of Agricultural Development, Agri-food & Management of Natural Resources, National and Kapodistrian University of Athens, Evripos Campus, Psachna, Evia, 34400, Greece.",
    "Institute of Pathobiochemistry, University Medical Center Mainz, Mainz, Germany.",
    "Tissue Biology and Therapeutic Engineering Laboratory (LBTI-UMR 5305 CNRS), Lyon University, Lyon, France.",
    "Molecular Neurodegeneration, Institute of Pathobiochemistry, University Medical Center Mainz, Mainz, Germany.",
    "Dept. of Immunology and Regenerative Biology, Weizmann Institute of Science, Max and Lillian Candiotty Building, Room 207, 234 Herzl St. Rehovot, Rehovot, 76100, Israel. irit.sagi@weizmann.ac.il.",
    "Biochemical Institute, Unit for Degradomics of the Protease Web, Kiel University, Otto-Hahn-Platz 9, Kiel, 24118, Germany. cbeckerpauly@biochem.uni-kiel.de."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Fred Armbrust"
    },
    {
      "affs": [
        0
      ],
      "name": "Hannah Bruhn"
    },
    {
      "affs": [
        0
      ],
      "name": "Kira Bickenbach"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicolas Steen"
    },
    {
      "affs": [
        1
      ],
      "name": "Sapir Shcoory"
    },
    {
      "affs": [
        2
      ],
      "name": "Nikolaos Afratis"
    },
    {
      "affs": [
        0
      ],
      "name": "Nele Korn"
    },
    {
      "affs": [
        3
      ],
      "name": "Hagen Körschgen"
    },
    {
      "affs": [
        4
      ],
      "name": "Catherine Moali"
    },
    {
      "affs": [
        5
      ],
      "name": "Claus U Pietrzik"
    },
    {
      "affs": [
        6
      ],
      "name": "Irit Sagi"
    },
    {
      "affs": [
        7
      ],
      "name": "Christoph Becker-Pauly",
      "orcid": "0000-0002-5100-9916"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e75yqsqvy8pvb.bib",
  "cited_by": 0,
  "doi": "10.1007/s00018-026-06361-4",
  "fulltext_url": "https://europepmc.org/articles/PMC13680589",
  "id": "e75yqsqvy8pvb",
  "issns": [
    "1420-682X",
    "1420-9071"
  ],
  "landing_url": "https://hal.science/hal-05762009v1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "lcc",
      "QH301-705.5"
    ],
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      "lcc",
      "QR1-502"
    ],
    [
      "openalex",
      "1306|Protease and Inhibitor Mechanisms"
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  "pdf_url": "https://hal.science/hal-05762009/document",
  "pmcid": "PMC13680589",
  "pmid": "42897323",
  "published": "2026-07-01",
  "publisher": "Springer Verlag",
  "ris": "https://research.draconitic.com/paper/e75yqsqvy8pvb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:00Z",
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    {
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      "native_id": "MED:42897323",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897323"
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    {
      "first_seen": "2026-10-30T13:45:41Z",
      "native_id": "00bd70604b19434daabec91a2a7279be",
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      "url": "https://doi.org/10.1007/s00018-026-06361-4"
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  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Protease and Inhibitor Mechanisms",
      "subfield": "oncology"
    }
  ],
  "title": "Meprin β is specifically inhibited by its cognate synthetic propeptide",
  "title_text": "Meprin β is specifically inhibited by its cognate synthetic propeptide",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T14:20:41Z",
  "url": "https://research.draconitic.com/paper/e75yqsqvy8pvb",
  "venue": "Cellular and Molecular Life Sciences",
  "versions": []
}