Neuronal STAT1 as a phase switch from antiviral defense to synaptopathy in encephalitis
Year: 2026
Type: review
Abstract: Interferon signaling is essential for antiviral defense in the central nervous system, yet sustained neuronal STAT1 phosphorylation (pSTAT1) can promote immune-mediated synaptic and network injury. In this opinion article, we argue that neuronal pSTAT1 functions as a context-dependent switch across viral and autoimmune encephalitis, shifting from antiviral protection to durable synaptopathy and excitability changes when interferon signaling persists. Integrating mechanistic, epigenomic, and translational evidence from mouse models and human neuropathology, we propose that prolonged neuronal pSTAT1 drives a durable synaptopathic program by silencing synaptic gene networks and epigenetic 'locking' of dysfunctional circuits. We discuss therapeutic opportunities and risks of targeting the JAK-STAT1 axis, emphasizing the trade-off between neuroprotection and antiviral immunity.
Source: Trends in Neurosciences
Authors: Giovanni Di Liberto, Doron Merkler
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $7,030
Funders: National Science Foundation, Schweizerischen Neurologischen Gesellschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Novartis Stiftung für Medizinisch-Biologische Forschung, Université de Lausanne, Schweizerische Multiple Sklerose Gesellschaft, Oral Reconstruction Foundation, Research Council, Rutgers, The State University of New Jersey, European Research Council, Faculté de Biologie et de Médecine, Université de Lausanne
OpenAlex ID: W7161013316