title: Glucocorticoid-Induced Leucine Zipper in Central Nervous System Health and Disease.
abstract: The central nervous system (CNS) is a large network of intercommunicating cells that function to maintain tissue health and homeostasis. Considerable evidence suggests that glucocorticoids exert both neuroprotective and neurodegenerative effects on the CNS. Glucocorticoids act by binding two related receptors in the cytoplasm, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). The glucocorticoid receptor complex mediates cellular responses by transactivating target genes and by protein: protein interactions. The paradoxical effects of glucocorticoids on neuronal survival and death have been attributed to the concentration and the ratio of mineralocorticoid to glucocorticoid receptor activation. Glucocorticoid-induced leucine zipper (GILZ) is a recently identified protein transcriptionally upregulated by glucocorticoids. Constitutively, expressed in many tissues including brain, GILZ mediates many of the actions of glucocorticoids. It mimics the anti-inflammatory and anti-proliferative effects of glucocorticoids but exerts differential effects on stem cell differentiation and lineage development. Recent experimental data on the effects of GILZ following induced stress or trauma suggest potential roles in CNS diseases. Here, we provide a short overview of the role of GILZ in CNS health and discuss three potential rationales for the role of GILZ in Alzheimer's disease pathogenesis.
authors.affiliation: Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, Indianapolis, IN, USA. mysriniv@iupui.edu.
authors.forename: Mythily
authors.identifier: http://orcid.org/0000-0003-1431-8215
authors.initials: M
authors.lastname: Srinivasan
authors.affiliation: Institute of Psychiatry Research, Department of Psychiatry and Medical & Molecular Genetics, School of Medicine, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA. dlahiri@iupui.edu.|Indiana Alzheimer Disease Center (IADC), Neuroscience Research Center, 320 West 15th Street, NB 200C, Indianapolis, IN, 46202-2266, USA. dlahiri@iupui.edu.
authors.forename: Debomoy K
authors.initials: DK
authors.lastname: Lahiri
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D016350:Leucine Zippers / Q000187:drug effects*; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid
keywords: Alzheimer’s disease; Glucocorticoid-induced leucine zipper; Glucocorticoids