Enhancing autophagy with drugs or lung-directed gene therapy reverses the pathological effects of respiratory epithelial cell proteinopathy

Abstract

Background: Several rare lung proteinopathies are characterized by lung fibrosis due to accumulation of misfolded proteins in epithelial cells. Results: The PiZ mouse models the pathological characteristics of these lung proteinopathies, and the pathology is ameliorated by autophagy enhancing therapies. Conclusion: Autophagy represents a key proteostasis mechanism for lung proteinopathies and a potential therapeutic target. Significance: The PiZ mouse is an attractive animal model of lung proteinopathies.