Pyroptosis targeting via mitochondria: An educated guess to innovate COVID-19 therapies.

Autor: Singh A; Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, UK., Strobbe D; Department of Biology, University of Rome 'Tor Vergata', Rome, Italy., Campanella M; Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, UK.; Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.; Department of Cell and Developmental Biology, Consortium for Mitochondrial Research (CfMR), University College London, London, UK.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2022 May; Vol. 179 (10), pp. 2081-2085. Date of Electronic Publication: 2021 Oct 10.
DOI: 10.1111/bph.15670
Abstrakt: Pyroptosis is a specialized form of inflammatory cell death which aids the defensive response against invading pathogens. Its normally tight regulation is lost during infection by the severe acute respiratory coronavirus 2 (SARS-CoV-2), and thus, uncontrolled pyroptosis disrupts the immune system and the integrity of organs defining the critical conditions in patients with high viral load. Molecular pathways engaged downstream of the formation and stabilization of the inflammasome, which are necessary to execute the process, have been uncovered and drugs are available for their regulation. However, the pharmacology of the upstream events, which are critical to sense and interpret the initial damage by the pathogen, is far from being elucidated. This limits our capacity to identify early markers and targets to ameliorate SARS-CoV-2 linked pyroptosis. Here, we focus attention on the mitochondria and pathways leading to their dysfunction, in order to elucidate the early steps of inflammasome formation and devise tools to predict and counter pathological states induced by SARS-CoV-2. LINKED ARTICLES: This article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc.
(© 2021 The British Pharmacological Society.)
Databáze: MEDLINE
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