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). — CFSMEATLAS
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).
Gottschalk, Gunnar, Peterson, Daniel, Knox, Konstance et al. · Molecular and cellular neurosciences · 2022 · DOI
Quick Summary
Researchers found that people with ME/CFS have higher levels of a protein called ATG13 in their blood compared to healthy people. When they tested this protein on brain immune cells in the lab, it triggered the production of harmful molecules called free radicals (oxidative stress). This suggests that a breakdown in the body's cellular recycling system (autophagy) might contribute to the inflammation and stress response seen in ME/CFS.
Why It Matters
This study identifies a specific molecular pathway—ATG13-RAGE signaling in microglial cells—that may explain how brain inflammation develops in ME/CFS. Understanding this mechanism could open new avenues for targeted treatments and biomarker development, potentially offering patients therapeutic options beyond symptom management.
Observed Findings
ATG13 protein levels are significantly elevated in serum of ME/CFS patients compared to age-matched healthy controls
ME/CFS patient serum triggers production of reactive oxygen species (ROS) and nitric oxide in human microglial cells
Neutralization of ATG13 in serum substantially reduces ROS and nitric oxide production in microglial cells
ATG13 binds to and activates RAGE (receptor for advanced glycation end products) on microglial cells
RAGE activation by ATG13 is associated with the oxidative stress response in microglia
Inferred Conclusions
Autophagy impairment, indicated by elevated serum ATG13, may represent a pathological signal in ME/CFS
ATG13-RAGE interaction on microglial cells contributes to the generation of oxidative stress and neuroinflammation observed in ME/CFS
Targeting the ATG13-RAGE pathway could potentially reduce the microglial activation and oxidative stress associated with ME/CFS
Remaining Questions
Does elevated ATG13 drive disease pathology in vivo, or is it a consequence of other disease mechanisms?
Do other tissues and cell types besides microglia respond to elevated ATG13, and what are the system-wide effects?
What This Study Does Not Prove
This study does not prove that ATG13 is the primary cause of ME/CFS or that blocking ATG13 will treat the disease in patients. It is an in vitro laboratory study, so findings may not translate directly to what happens in living patients. The study shows correlation and a possible mechanism, but clinical trials would be needed to establish whether targeting this pathway benefits patients.