CNS disease associated with enhanced type I interferon signalling

The ability to mount an interferon-mediated innate immune response is essential in protection against neurotropic viruses, but antiviral type 1 interferons also have neurotoxic potential. Production of type 1 interferons can be triggered by self-derived nucleic acids and the brain can be susceptible to inappropriate upregulation of type 1 interferon signalling. Homeostatic regulation of type 1 interferons has been implicated in the context of both rare inborn errors of immunity, referred to as the type 1 interferonopathies, and more common neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. Recent developments include new insights into the pathogenesis of these disorders seen in both paediatric and adult practice, as well as into their diagnosis and management. The role of type 1 interferons in brain cellular health implies the future therapeutic potential of approaches that target these interferons and their signaling.