The integrated stress response in pulmonary disease. (1st October 2020)

• Record Type: Journal Article
• Authors: Emanuelli, Giulia; Nassehzadeh-Tabriz, Nikou; Morrell, Nick W.; Marciniak, Stefan J.
• Is Part Of: European respiratory review. Volume 29:Number 157(2020)
• Publication Date: 2020-10-01
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases; Respiratory organs -- Diseases; Respiratory organs -- Diseases -- Treatment; Electronic journals; Periodical; Periodicals; Periodicals; 616.2
• DOI: 10.1183/16000617.0184-2020
• Languages: English
• ISSNs: 0905-9180

Abstract

The respiratory tract and its resident immune cells face daily exposure to stress, both from without and from within. Inhaled pathogens, including severe acute respiratory syndrome coronavirus 2, and toxins from pollution trigger a cellular defence system that reduces protein synthesis to minimise viral replication or the accumulation of misfolded proteins. Simultaneously, a gene expression programme enhances antioxidant and protein folding machineries in the lung. Four kinases (PERK, PKR, GCN2 and HRI) sense a diverse range of stresses to trigger this "integrated stress response". Here we review recent advances identifying the integrated stress response as a critical pathway in the pathogenesis of pulmonary diseases, including pneumonias, thoracic malignancy, pulmonary fibrosis and pulmonary hypertension. Understanding the integrated stress response provides novel targets for the development of therapies. By integrating signals from multiple stressors, the integrated stress response plays key roles in the pathophysiology of lung disease. Understanding the mechanisms involved will identify novel means of therapy. https://bit.ly/2Bg2kj4