Preclinical and translational studies suggest that ER-β and GPER1 activation enhances brain-derived neurotrophic factor (BDNF) expression, modulates CREB and PI3K/Akt pathways, and attenuates interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) signaling—mechanisms dysregulated in TR-BD. This evidence concerns the gene TNF and Behcet disease.