Uncovering the role of MEGF6 in Aicardi-Goutières Syndrome neuroinflammation

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2025.

Aicardi-Goutières Syndrome (AGS) is a rare genetic brain disease that affects children, causing severe neurological problems. It occurs due to mutations in genes that help process DNA and RNA, leading to harmful immune system activation. However, we still don’t fully understand how AGS damages brain cells, partly because animal models don’t accurately mimic the disease in humans. To study AGS more effectively, we created mimics of the disease in human brain cells using stem cell technologies. We found that certain brain cells, called astrocytes, contribute to nerve cell damage by triggering inflammation and DNA damage responses. Additionally, we identified that AGS astrocytes release a set of little-known proteins, called Tdarks, that might play a role in brain inflammation. Since one of these Tdarks has been linked to other brain conditions, we suspect it could be involved in AGS as well. Our research will explore the role of this selected Tdark in AGS, which could help us discover new treatments to slow or prevent this devastating disease.