Neurobiological Insights into Depression: The STAT3 Signaling Pathway as a Therapeutic Target

Signal Transducer and Activator of Transcription 3 (STAT3), a significant component of the STAT family, is vital for cellular signal transduction and gene expression regulation. STAT3 is capable of interacting with cytokine receptors, facilitating signal transduction to the nucleus, where it modulates the transcriptional activity of downstream target genes. Notably, STAT3 exhibits dual roles depending on its activation state: physiologically activated STAT3 contributes to neuroprotection, promotes neurogenesis, and inhibits inflammation, whereas under pathological conditions, overactivated STAT3 exacerbates neuroinflammation, induces apoptosis, and disrupts synaptic function. Recent research has discovered that the STAT3 signaling pathway is crucial in the occurrence and development of depression. This article reviews the mechanism of the STAT3 signaling pathway in depression, including its regulatory role in neuroinflammation, neurogenesis, apoptosis, synaptic function, and hormone regulation. In particular, the article analyzed in detail the activation of STAT3 in the JAK/STAT pathway, which has a crucial impact on cell proliferation, differentiation, survival, and apoptosis, and thus regulates neuronal survival and function in the nervous system. In addition, we highlighted the potential advantages of STAT3 as a multi-target regulatory center in anti- inflammation, the promotion of neural regeneration, and the improvement of synaptic function, and suggested that combining it with conventional antidepressants may enhance the therapeutic effect, thus paving a new way for personalized and precise treatment. We have reviewed previous studies on the link between STAT3 signaling and depression and evaluated the value of STAT3 signaling as a therapeutic target for depression, with a view to providing a novel direction for the development of treatment strategies for depression.