Microglial activating transcription factor 3 upregulation: An indirect target to attenuate inflammation in the nervous system

Activating Transcription Factor 3 (ATF3) responds to cellular stressors in various conditions, coordinating a transcriptional response. It's critical for axon regeneration in the peripheral nervous system and a target for mitigating regenerative failure in the central nervous system. In immunology, ATF3 is a master regulator of the innate immune system, suppressing inflammation in macrophages after activation by pathogens or damage. ATF3 upregulation can be achieved through small molecule administration. In the central nervous system, microglia are resident macrophages. Inducing ATF3 expression in microglia could dampen inflammatory microglial phenotype, offering therapeutic benefits, especially in conditions like spinal cord injury, multiple sclerosis, and stroke.

• 1
  ATF3 functions as a negative regulator of innate immune activation, suppressing pro-inflammatory gene expression in macrophages following TLR4 activation.
• 2
  ATF3 regulates the macrophage interferon (IFN) response to microbial infection, with ATF3 deficient macrophages showing increased IFNβ production upon TLR3 or STING stimulation.
• 3
  ATF3 upregulation is achievable through small molecules, making it a potential indirect drug target for mitigating microglial inflammatory responses in CNS diseases.