Project Information

Modulation of RELB/p52-dependent NF-KB activities to improve neurodegenerative
symptoms of AT

SCIENTIFIC LEAD: Dr Svetlana Khorenenkova, Cambridge University, UK

LENGTH: Concluded

COSTS: £90,000

Svetlana’s project concluded in 2024 and involved investigating why AT brain cells are damaged, focusing especially on the role of microglia, a type of brain immune cell. Svetlana’s team found that microglia become chronically inflamed, disrupting their normal supportive functions and leaving surrounding brain cells vulnerable, and that a key factor driving these harmful changes is the cGAS-STING immune pathway.

When the ATM gene, which is defective in AT, is missing or malfunctioning, microglia are less effective at monitoring brain health. Svetlana revealed that reducing inflammation—either by removing the STING component or by using experimental drugs—helped restore normal microglial function, suggesting that unchecked inflammation impairs the development of synaptic connections between nerve cells, a process crucial for brain development and movement regulation. ATM-deficient microglia also appear to engulf too many synapses, potentially exacerbating neural network problems.

The study’s contribution to clarifying how AT leads to brain cell damage and indicates that targeting the cGAS-STING pathway to reduce inflammation might be a promising therapeutic strategy, is significant. It contributes to a growing body of work that could soon lead to clinical trials to improve neurological outcomes for children with AT.