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Chronic inflammation is a prolonged, dysregulated immune response that persists for weeks to years when the inciting stimulus is difficult to eradicate or when self‑antigens drive ongoing reactivity. Morphologically, it is defined by mononuclear cell infiltration, progressive tissue destruction, and concurrent attempts at healing via angiogenesis and fibrosis. Compared with acute inflammation, edema is less prominent while cellular infiltration predominates; triggers include persistent...
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Inflammation-mediating proteases: structure, function in (patho) physiology and inhibition.

Mateja Mancek-Keber1

  • 1National Institute of Chemistry, Ljubljana, Slovenia; EN→FIST Centre of Excellence, 1000 Ljubljana, Slovenia. mateja.mancek@ki.si.

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Proteases regulating inflammation, like ADAMTS and granzymes, are key enzymes in physiological processes. Their dysregulation drives inflammatory diseases, making protease inhibitors a promising therapeutic strategy.

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Area of Science:

  • Enzymology
  • Molecular Biology
  • Immunology

Background:

  • Proteases are enzymes crucial for physiological processes including wound healing and angiogenesis.
  • Dysregulated protease activity and increased expression during inflammation contribute to various diseases.
  • These enzymes play roles in vascular diseases, inflammatory arthritis, cancer, and allograft rejection.

Purpose of the Study:

  • To review the roles of specific proteases in inflammation and inflammatory diseases.
  • To discuss the physiological functions and disease-associated mechanisms of proteases.
  • To explore protease inhibitors as a therapeutic approach.

Main Methods:

  • Literature review of proteases involved in inflammation.
  • Analysis of physiological roles and pathological contributions of proteases.
  • Examination of protease inhibitor strategies.

Main Results:

  • Several proteases, including ADAMTS, granzymes, plasmin, and kallikreins, were described.
  • Their diverse mechanisms and substrates in inflammation were detailed.
  • The potential of protease inhibition for treating inflammatory conditions was highlighted.

Conclusions:

  • Proteases are critical regulators of inflammation with significant roles in disease pathogenesis.
  • Targeting these enzymes with inhibitors offers a viable therapeutic avenue.
  • Further research into physiological and engineered inhibitors is warranted.