Figure 1.

The contribution of Sigma1R activation in intracellular mechanisms of the antidepressant effect. The figure represents chaperone interactions of Sigma1R and functional consequences on proteins triggered by Sigma1R activation. Interaction of Sigma1R with BDNF receptor, GluN, Ca²⁺ channels, and ER stress sensor promotes activation of signal cascades and Ca²⁺-dependent proteins. These processes jointly with Sigma1R-dependent epigenetic regulation cause changes in expression of genes of neurotrophins, chaperones, proteins of antioxidant defense, and cytokines that provide the antidepressant effect. Plain arrow—Ca²⁺ flux; dashed arrow—Sigma1R-mediated influences. Akt1—RAC-alpha serine/threonine-protein kinase; ASIC—Acid-sensing ion channel; BDNF—Brain-derived neurotrophic factor; BiP—Endoplasmic reticulum chaperone BiP; CaMKIIα—Calcium/calmodulin-dependent protein kinase II alpha; CaMKIV—Calcium/calmodulin-dependent protein kinase type IV; CREB—Cyclic AMP-responsive element-binding protein; GluN—Glutamate receptor ionotropic, NMDA; GSK-3β—Glycogen synthase kinase-3 beta; IP3R1— Inositol 1,4,5-trisphosphate receptor type 1; IP3R3—Inositol 1,4,5-trisphosphate receptor type 3; IRE1—Serine/threonine-protein kinase/endoribonuclease IRE1; miRNA—Small non-coding microRNA; NGF—Beta-nerve growth factor; PI3K—Phosphatidylinositol 3-kinase; PLCγ—1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma; trkA—High affinity nerve growth factor receptor; trkB—BDNF/NT-3 growth factors receptor; neurotrophic receptor tyrosine kinase 2; UPR—Unfolded protein response; XBP1—X-box-binding protein 1.