Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE).

Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS), is a multisystem illness characterized by extreme muscle fatigue associated with pain, neurocognitive impairment, and chronic inflammation. Despite intense investigation, the molecular mechanism of this disease is still unknown. Here we demonstrate that autophagy-related protein ATG13 is strongly upregulated in the serum of ME/CFS patients, indicative of impairment in the metabolic events of autophagy. A Thioflavin T-based protein aggregation assay, array screening for autophagy-related factors, densitometric analyses, and confirmation with ELISA revealed that the level of ATG13 was strongly elevated in serum samples of ME/CFS patients compared to age-matched controls. Moreover, our microglia-based oxidative stress response experiments indicated that serum samples of ME/CFS patients evoke the production of reactive oxygen species (ROS) and nitric oxide in human HMC3 microglial cells, whereas neutralization of ATG13 strongly diminishes the production of ROS and NO, suggesting that ATG13 plays a role in the observed stress response in microglial cells. Finally, an in vitro ligand binding assay provided evidence that ATG13 employs the Receptor for Advanced Glycation End-products (RAGE) to stimulate ROS in microglial cells. Collectively, our results suggest that an impairment of autophagy following the release of ATG13 into serum could be a pathological signal in ME/CFS.

ACE2: At the crossroad of COVID-19 and lung cancer.

Upregulation of Angiotensin Converting Enzyme-2 (ACE2) was frequently observed in patients with lung cancer. Interestingly, our recent study revealed that the same ACE2 receptor was also strongly upregulated in lungs during SARS-CoV2 infection. Therefore, it is possible that the upregulated expression of ACE2 in lung tumors might increase the susceptibility to COVID-19 infection in lung cancer patients. However, the molecular mechanism for the regulation of ACE2 is known neither in lung tumors nor in COVID-19. Under this review, we attempt to identify transcription factors (TFs) in the promoter of ACE2 that promote the expression of ACE2 both in COVID-19 infection and lung cancer. This review would decipher the molecular role of ACE2 in the upscaled fatality of lung cancer patients suffering from COVID-19.