Abstract
This review analyzes the current scientific literature on the role of the Sigma1R chaperone in the pathogenesis of depressive disorders and pharmacodynamics of antidepressants. As a result of ligand activation, Sigma1R is capable of intracellular translocation from the endoplasmic reticulum (ER) into the region of nuclear and cellular membranes, where it interacts with resident proteins. This unique property of Sigma1R provides regulation of various receptors, ion channels, enzymes, and transcriptional factors. The current review demonstrates the contribution of the Sigma1R chaperone to the regulation of molecular mechanisms involved in the antidepressant effect.
Highlights
The incidence of depressive disorders is growing steadily and represents an acute medical and social problem [1]
The current review demonstrates the contribution of the sigma-1 receptors (Sigma1R) chaperone to the regulation of molecular mechanisms involved in the antidepressant effect
The client proteins of the Sigma1R chaperone are involved in the pathogenesis of depressive disorders [76,77,78,79,80,81,82,83], which indicates the importance of Sigma1R for the pharmacodynamics of antidepressants
Summary
The incidence of depressive disorders is growing steadily and represents an acute medical and social problem [1]. Antidepressants used in clinical practice have proved their efficacy in long-term treatment [2] Such medication is accompanied by various side effects [3], and about one-third of patients do not achieve remission [4]. An attempt to introduce selective Sigma1R agonists into clinical practice as antidepressant drugs was unsuccessful [32,33,34]. Despite these findings, discoveries in molecular biology have revealed three important properties of Sigma1R: chaperone activity aimed at a large number of proteins, intracellular translocation within lipid microdomains, and interaction with a large number of chemical compounds [35,36,37]. This review aims to highlight the role of the chaperone Sigma1R in the pathogenesis of depression and the pharmacodynamics of antidepressants
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