Journal Article

Autophagy Augmentation to Alleviate Immune Response Dysfunction, and Resolve Respiratory and COVID-19 Exacerbations

Pehote, Garrett, Vij, Neeraj

2020

Overview

The preservation of cellular homeostasis requires the synthesis of new proteins (proteostasis) and organelles, and the effective removal of misfolded or impaired proteins and cellular debris. This cellular homeostasis involves two key proteostasis mechanisms, the ubiquitin proteasome system and the autophagy–lysosome pathway. These catabolic pathways have been known to be involved in respiratory exacerbations and the pathogenesis of various lung diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and coronavirus disease-2019 (COVID-19). Briefly, proteostasis and autophagy processes are known to decline over time with age, cigarette or biomass smoke exposure, and/or influenced by underlying genetic factors, resulting in the accumulation of misfolded proteins and cellular debris, elevating apoptosis and cellular senescence, and initiating the pathogenesis of acute or chronic lung disease. Moreover, autophagic dysfunction results in an impaired microbial clearance, post-bacterial and/or viral infection(s) which contribute to the initiation of acute and recurrent respiratory exacerbations as well as the progression of chronic obstructive and restrictive lung diseases. In addition, the autophagic dysfunction-mediated cystic fibrosis transmembrane conductance regulator (CFTR) immune response impairment further exacerbates the lung disease. Recent studies demonstrate the therapeutic potential of novel autophagy augmentation strategies, in alleviating the pathogenesis of chronic obstructive or restrictive lung diseases and exacerbations such as those commonly seen in COPD, CF, ALI/ARDS and COVID-19.

• Publisher: MDPI AG,MDPI
• Subject: Acute Lung Injury - immunology / Acute Lung Injury - metabolism / Aging / ALI / Apoptosis / ARDS / Autophagy / Autophagy (Cytology) / Autophagy - immunology / Betacoronavirus / Chronic obstructive pulmonary disease / Conductance / COPD / Coronavirus Infections - immunology / Coronavirus Infections - metabolism / Coronavirus Infections - virology / Coronaviruses / COVID-19 / Cystic fibrosis / Cystic Fibrosis - immunology / Cystic Fibrosis - metabolism / Cystic Fibrosis Transmembrane Conductance Regulator - metabolism / Disease Progression / Emphysema / exacerbations / Genetic factors / Health aspects / Homeostasis / Humans / Idiopathic Pulmonary Fibrosis - immunology / Idiopathic Pulmonary Fibrosis - metabolism / Immune clearance / Immune response / Infections / Inflammation / Lipids / Lung diseases / Lymphocytes / Lysosomes - metabolism / Mortality / Observations / Obstructive lung disease / Organelles / Oxidative stress / Pandemics / Pathogenesis / Pathogens / Phagocytosis / Physiological aspects / Pneumonia, Viral - immunology / Pneumonia, Viral - metabolism / Pneumonia, Viral - virology / Preservation / Proteasomes / Protein folding / Proteins / Pulmonary Disease, Chronic Obstructive - immunology / Pulmonary Disease, Chronic Obstructive - metabolism / Recurrent infection / Respiratory diseases / Respiratory distress syndrome / Respiratory Distress Syndrome - immunology / Respiratory Distress Syndrome - metabolism / Respiratory syncytial virus / Review / SARS-CoV-2 / Senescence / Ubiquitin / Viral infections / Viruses