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Journal Article

Lung protection by cathepsin C inhibition: A new hope for COVID-19 and ARDS?

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Jenne,  Dieter E.
Emeritus Group: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

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Citation

Korkmaz, B., Lesner, A., Marchand-Adam, S., Moss, C., & Jenne, D. E. (2020). Lung protection by cathepsin C inhibition: A new hope for COVID-19 and ARDS? Journal of Medicinal Chemistry, 63(22), 13258-13265. doi:10.1021/acs.jmedchem.0c00776.


Cite as: https://hdl.handle.net/21.11116/0000-0009-9F18-A
Abstract
Cathepsin C (CatC) is a cysteine dipeptidyl aminopeptidase that
activates most of tissue-degrading elastase-related serine proteases.
Thus, CatC appears as a potential therapeutic target to impair
protease-driven tissue degradation in chronic inflammatory and
autoimmune diseases. A depletion of proinflammatory elastase-related
proteases in neutrophils is observed in patients with CatC deficiency
(Papillon-Lefevre syndrome). To address and counterbalance unwanted
effects of elastase-related proteases, chemical inhibitors of CatC are
being evaluated in preclinical and clinical trials. Neutrophils may
contribute to the diffuse alveolar inflammation seen in acute
respiratory distress syndrome (ARDS) which is currently a growing
challenge for intensive care units due to the outbreak of the COVID-19
pandemic. Elimination of elastase-related neutrophil proteases may
reduce the progression of lung injury in these patients. Pharmacological
CatC inhibition could be a potential therapeutic strategy to prevent the
irreversible pulmonary failure threatening the life of COVID-19
patients.