title: Modulation of c-Jun N-terminal kinase signaling and specific glucocorticoid receptor phosphorylation in the treatment of major depression.
abstract: Glucocorticoid resistance is a common finding in major depressive disorder. Increased glucocorticoid receptor (GR) phosphorylation at serine 226 is associated with increased glucocorticoid resistance. Previously we have demonstrated that depressed patients exhibit higher levels of GR phosphorylated at serine 226 compared to healthy controls. The enzyme that is involved in this specific GR phosphorylation is c-Jun N-terminal kinase (JNK). We propose that modulation of glucocorticoid phosphorylation at serine 226, by targeting JNK signaling pathway, could be a potential strategy for antidepressant treatment. We base this assumption on the results of previous research that examined GR phosphorylation and JNK signaling in animal models and human studies. We also discuss the potential challenges in targeting JNK signaling pathway in depression.
authors.affiliation: School of Medicine, University of Belgrade, Serbia.
authors.forename: Milica J
authors.initials: MJ
authors.lastname: Jovicic
authors.affiliation: Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, Serbia.
authors.forename: Iva
authors.initials: I
authors.lastname: Lukic
authors.affiliation: Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Radojcic
authors.affiliation: Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, Serbia.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Adzic
authors.affiliation: School of Medicine, University of Belgrade, Serbia; Clinic for Psychiatry, Clinical Center of Serbia, Belgrade, Serbia. Electronic address: nadjamaric@yahoo.com.
authors.forename: Nadja P
authors.initials: NP
authors.lastname: Maric
mesh_terms: D003865:Major Depressive Disorder / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011965:Receptors, Glucocorticoid; D048031:JNK Mitogen-Activated Protein Kinases