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

Abstract

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.

Astaxanthin and its Effects in Inflammatory Responses and Inflammation-Associated Diseases: Recent Advances and Future Directions

“…In Pacific white shrimp, astaxanthin could promote the mRNA expression of antioxidant enzyme gene and increase the resistance to white spot syndrome virus (WSSV) [ 89 ]. Significantly, since the pathogenesis and complications of many viral infectious diseases such as coronavirus disease 2019 (COVID-19) are also involved in the role of oxidative stress, inflammation, apoptosis, and autophagy [ 90 , 91 , 92 ], astaxanthin may be a promising candidate in combating viral infectious diseases. However, it’s not clear at present whether the anti-inflammatory effects of astaxanthin or other functions of astaxanthin, such as antioxidative, anti-apoptosis, and autophagy-modulatory activities, have a protective effect for viral infectious diseases, especially for COVID-19 infection.…”

Covid-19-Associated Pulmonary Aspergillosis: The Other Side of the Coin

“…Indeed, thymosin α1 could either be immunostimulatory, such as in cancer and immune deficiency, or promote tolerance in inflammatory conditions, for instance by inducing the indoleamine 2,3-dioxygenase 1 pathway [ 67 , 68 , 69 ] or promoting autophagy [ 68 ]. The latter process is increasingly being recognized as a regulator of lung health and protection against microbial infection, with potential relevance for a variety of lung diseases, including COVID-19 [ 70 ]. Of interest, thymosin α1 has already proven to be beneficial in the protection against viral [ 71 ] and fungal [ 72 ] infections, by promoting an IFN response and a protective Th1 resistance, respectively.…”

The networks of m6A-SARS-CoV-2 related genes and immune infiltration patterns in idiopathic pulmonary fibrosis

“…There is some overlap in the progress between COVID-19 and pulmonary fibrosis [ 10 – 12 ]. In addition, IPF is a risk factor for COVID-19 as IPF patients have a higher expression of some SARS-CoV-2 related genes, which may play a crucial role in SARS-CoV-2 entry, processing, and attachment [ 13 , 14 ].…”