Poly(ADP-Ribose) Polymerase Inhibition in Acute Lung Injury. A Reemerging Concept.
Am J Respir Cell Mol Biol
; 63(5): 571-590, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32640172
ABSTRACT
PARP1, the major isoform of a family of ADP-ribosylating enzymes, has been implicated in the regulation of various biological processes including DNA repair, gene transcription, and cell death. The concept that PARP1 becomes activated in acute lung injury (ALI) and that pharmacological inhibition or genetic deletion of this enzyme can provide therapeutic benefits emerged over 20 years ago. The current article provides an overview of the cellular mechanisms involved in the pathogenetic roles of PARP1 in ALI and provides an overview of the preclinical data supporting the efficacy of PARP (poly[ADP-ribose] polymerase) inhibitors. In recent years, several ultrapotent PARP inhibitors have been approved for clinical use (for the therapy of various oncological diseases) these newly-approved PARP inhibitors were recently reported to show efficacy in animal models of ALI. These observations offer the possibility of therapeutic repurposing of these inhibitors for patients with ALI. The current article lays out a potential roadmap for such repurposing efforts. In addition, the article also overviews the scientific basis of potentially applying PARP inhibitors for the experimental therapy of viral ALI, such as coronavirus disease (COVID-19)-associated ALI.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Pneumonia Viral
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Infecções por Coronavirus
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Lesão Pulmonar Aguda
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Inibidores de Poli(ADP-Ribose) Polimerases
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Poli(ADP-Ribose) Polimerase-1
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Betacoronavirus
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Pulmão
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Am J Respir Cell Mol Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2020
Tipo de documento:
Article