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.

PARP1 是 ADP 核糖基化酶家族的主要亚型，参与多种生物过程的调节，包括 DNA 修复、基因转录和细胞死亡。PARP1 在急性肺损伤 (ALI) 中被激活，并且该酶的药理学抑制或基因删除可以提供治疗益处的概念早在 20 多年前就出现了。本文概述了 PARP1 在 ALI 中的发病机制，并概述了支持 PARP（聚[ADP-核糖]聚合酶）抑制剂功效的临床前数据。近年来，多种超强 PARP 抑制剂已被批准用于临床（用于治疗各种肿瘤疾病）：最近有报道称，这些新批准的 PARP 抑制剂在 ALI 动物模型中显示出疗效。这些观察结果为重新利用这些抑制剂治疗 ALI 患者提供了可能性。当前的文章为此类重新利用工作列出了潜在的路线图。此外，本文还概述了可能应用 PARP 抑制剂进行病毒性 ALI 实验治疗的科学依据，例如冠状病毒病 (COVID-19) 相关的 ALI。