CRF signaling: molecular specificity for drug targeting in the CNS
Corticotrophin-releasing factor (CRF) is the key mediator of the central nervous system response needed to adapt to stress. If adaptation fails, hypersecretion of CRF continues and produces, via CRF type 1 receptors, symptoms pertaining to cognition, appetite, sleep and anxiety, implicating CRF as a...
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2006
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| Acceso en línea: | Registro en Scopus DOI Handle Registro en la Biblioteca Digital |
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| 008 | 190411s2006 xx ||||fo|||| 00| 0 eng|d | ||
| 024 | 7 | |2 scopus |a 2-s2.0-33748575313 | |
| 024 | 7 | |2 cas |a calcium ion, 14127-61-8; corticotropin releasing factor, 9015-71-8; mitogen activated protein kinase, 142243-02-5; nitric oxide synthase, 125978-95-2; phorbol 13 acetate 12 myristate, 16561-29-8; phospholipase C, 9001-86-9; Corticotropin-Releasing Hormone, 9015-71-8 | |
| 040 | |a Scopus |b spa |c AR-BaUEN |d AR-BaUEN | ||
| 030 | |a TPHSD | ||
| 100 | 1 | |a Arzt, E. | |
| 245 | 1 | 0 | |a CRF signaling: molecular specificity for drug targeting in the CNS |
| 260 | |c 2006 | ||
| 270 | 1 | 0 | |m Arzt, E.; Laboratorio de Fisiología y Biología Molecular, Departamento Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales (FCEN), 1428 Buenos Aires, Argentina |
| 506 | |2 openaire |e Política editorial | ||
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| 520 | 3 | |a Corticotrophin-releasing factor (CRF) is the key mediator of the central nervous system response needed to adapt to stress. If adaptation fails, hypersecretion of CRF continues and produces, via CRF type 1 receptors, symptoms pertaining to cognition, appetite, sleep and anxiety, implicating CRF as a causal factor in affective disorders. Clinical studies with CRF receptor 1 antagonists support a novel pharmacological strategy for treating stress-related disorders. Here we summarize recent information obtained on CRF receptor 1 signaling and propose the concept of a more focused pharmacological intervention based on the signaling pathways involved. Recent findings suggest that CRF activates, via the same CRF receptor 1, different signaling pathways in specific areas of the brain. This intracellular and neuroanatomical signaling specificity will facilitate the search for less pleiotropic antagonists and new chemical compounds that modulate signal transduction in a site-specific manner. © 2006 Elsevier Ltd. All rights reserved. |l eng | |
| 536 | |a Detalles de la financiación: Agencia Nacional de Promoción Científica y Tecnológica | ||
| 536 | |a Detalles de la financiación: Universidad de Buenos Aires | ||
| 536 | |a Detalles de la financiación: Bristol-Myers Squibb Foundation | ||
| 536 | |a Detalles de la financiación: National Council for Scientific Research | ||
| 536 | |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas | ||
| 536 | |a Detalles de la financiación: We thank Damian Refojo for his support in assembling this review. E.A. is a member of the Argentine National Research Council, IFIBYNE, CONICET, Buenos Aires, Argentina. This work was supported by grants from the Max Planck Society, University of Buenos Aires, the Argentine National Research Council (CONICET) and Agencia Nacional de Promoción Científica y Tecnológica-Argentina. Part of this work was supported by the ‘Freedom to Discover Award’ given to F.H. by the Bristol-Myers Squibb Foundation. Affective disorders affective or mood disorders are mental disorders that primarily affect mood, interfere with the activities of daily living, and impair the lives of ∼10–15% of the worldwide population. They are severe stress-related psychiatric disorders and can include suicidal thoughts and suicide attempts. They encompass unipolar depression, bipolar disorder and anxiety disorders. Conditional gene targeting spatial and temporal control of selected transgenes by means of specific promoters and sophisticated recombination systems that enable the overexpression, reduction or deletion of targeted genes. Intracerebroventricular administration a method of delivering small amounts of substances (e.g. antisense oligonucleotides, double-stranded RNA for RNA-mediated interference, hormones, neurotransmitters and/or pharmacological compounds) directly into the cerebral ventricles. Limbic system a complex interconnected network of deep-lying forebrain structures including prefrontal cortex, the limbic lobe (containing the cingulate gyrus, parahippocampal gyrus and hippocampal formation) and other subcortical and diencephalic structures such as the septal area, the nucleus accumbens, the hypothalamus and the amygdala. This circuit manages several processes related to learning and memory, feelings and emotional behavior, including memory processing, emotional association with memory, motivation, judgment, affect and organization of planned actions. MAGUKs membrane-associated guanylate kinases. A family of proteins that function as scaffolds to assemble transmembrane and cytosolic proteins into supramolecular signaling complexes at specific cellular locations. MAPK signaling pathway a three-membered protein kinase signaling pathway that includes the protein kinases MAPKKK, MAPKK and MAPK. MAPK Mitogen-activated protein kinase. Protein kinases that respond to various extracellular signals. The main members of the MAPK family include extracellular-signal-regulated kinases (ERK1/2; also known as p42/p44); c-Jun amino-terminal kinase (JNK); p38 (p38 MAPK); MAPK kinases (MAPKKs), dual serine/tyrosine kinases that activate specific MAPK substrates; MAPK kinase kinase (MAPKKK), kinases (including the Raf family of proteins) that respond to various extracellular signals and elicit signal transduction mechanisms through phosphorylation of MAPKK; MEK1 and MEK2, MAPKKs that are specific ERK kinases; and Ras, a family of small GTP-binding proteins that activate numerous signaling molecules through their regulatory interaction with effectors such as Raf-1 and B-Raf. Neuroprotection a process that facilitates the survival of neuronal cells injured by different insults such as toxicity, infection and inflammatory processes, traumatic brain injury and stroke. NFκB nuclear factor-κB. A transcription factor that regulates the expression of genes involved in several cellular processes such as inflammation, cell proliferation and apoptosis. NOS nitric oxide synthase. An enzyme that catalyzes the formation of nitric oxide, a signaling molecule and a neurotransmitter, from oxygen and arginine. Nur77 orphan nuclear receptor, also known as nerve growth factor inducible B, that belongs to the Nur subfamily of transcription factors. PLC cascade binding of a hormone to its receptor leads to activation of the G protein G q , which in turn activates phosphatidylinositol-specific phospholipase C (PLC) by a mechanism analogous to activation of adenylyl cyclase. PLC hydrolyzes phosphatidylinositol (4,5)-bisphosphate to the second messengers 1,2-diacylglycerol and inositol (1,4,5)-trisphosphate, which facilitate membrane targeting of signaling enzymes through lipid binding and increase intracellular Ca 2+ , respectively. PKA cascade ligand binding to GPCRs activates a stimulatory G-protein (G s ) that interacts with adenylyl cyclase, causing accumulation of cAMP. Active cAMP-dependent protein kinase (PKA) catalytic subunits are released on binding of cAMP to the regulatory subunits. The catalytic subunits phosphorylate targets in the cytoplasm and the nucleus. In addition to PKA, components of the cascade include adenylyl cyclase, an enzyme that synthesizes cAMP on activation by a stimulatory G (G s ) protein; A-kinase anchoring proteins (AKAPs), adaptor proteins that keep PKA at specific cellular locations limiting the targets that can be phosphorylated by activated PKA; cAMP response element binding protein (CREB), the main transcriptional regulator activated by PKA phosphorylation that mediates PKA mechanisms involving gene expression; cAMP, a second messenger synthesized by adenylyl cyclase in response to external stimuli; and forskolin, a pharmacological agent that activates adenylyl cyclase directly, bypassing the need of an activated G s protein. PKC cascade a rise in cytosolic Ca 2+ recruits the serine/threonine protein kinase PKC from the cytosol to the membrane where it is activated by 1,2-diacylglycerol. The activated kinase then phosphorylates various target proteins that control growth and differentiation. Components of the PKC cascade include calmodulin, an intracellular Ca 2+ receptor that initiates various signaling cascades by binding to protein targets in a Ca 2+ -dependent manner; and 1,2-diacylglycerol and inositol (1,4,5)-trisphosphate, second messengers activated in response to a rise in cytosolic Ca 2+ . PMA phorbol-12-myristate-13 acetate. A phorbol ester that activates PKC. Stress the concept of stress was taken by Hans Selye from the physical sciences and defined as ‘the nonspecific response of the body to any demand upon it…’. According to the current concept, stress is a condition in which the homeostatic set points, genetically programmed or learned, do not match with the current or anticipated perception of the internal or external variables sensed. These discrepancies are then evaluated in terms of a real or predicted threat to homeostasis, triggering specific patterns of behavioral and physical adaptive responses. | ||
| 593 | |a Laboratorio de Fisiología y Biología Molecular, Departamento Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales (FCEN), 1428 Buenos Aires, Argentina | ||
| 593 | |a Max-Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany | ||
| 690 | 1 | 0 | |a CALCIUM ION |
| 690 | 1 | 0 | |a CORTICOTROPIN RELEASING FACTOR |
| 690 | 1 | 0 | |a CORTICOTROPIN RELEASING FACTOR RECEPTOR 1 |
| 690 | 1 | 0 | |a CYCLIC AMP DEPENDENT PROTEIN KINASE |
| 690 | 1 | 0 | |a IMMUNOGLOBULIN ENHANCER BINDING PROTEIN |
| 690 | 1 | 0 | |a MEMBRANE ASSOCIATED GUANYLATE CYCLASE KINASE |
| 690 | 1 | 0 | |a MITOGEN ACTIVATED PROTEIN KINASE |
| 690 | 1 | 0 | |a NITRIC OXIDE SYNTHASE |
| 690 | 1 | 0 | |a PHORBOL 13 ACETATE 12 MYRISTATE |
| 690 | 1 | 0 | |a PHOSPHOLIPASE C |
| 690 | 1 | 0 | |a RECEPTOR SUBTYPE |
| 690 | 1 | 0 | |a ADAPTATION |
| 690 | 1 | 0 | |a ADDICTION |
| 690 | 1 | 0 | |a ANXIETY DISORDER |
| 690 | 1 | 0 | |a BRAIN |
| 690 | 1 | 0 | |a CELL MEMBRANE PERMEABILITY |
| 690 | 1 | 0 | |a CENTRAL NERVOUS SYSTEM |
| 690 | 1 | 0 | |a DEPRESSION |
| 690 | 1 | 0 | |a DRUG TARGETING |
| 690 | 1 | 0 | |a HIPPOCAMPUS |
| 690 | 1 | 0 | |a HUMAN |
| 690 | 1 | 0 | |a HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM |
| 690 | 1 | 0 | |a LIMBIC CORTEX |
| 690 | 1 | 0 | |a MENTAL DISEASE |
| 690 | 1 | 0 | |a MOOD DISORDER |
| 690 | 1 | 0 | |a NEUROANATOMY |
| 690 | 1 | 0 | |a NEUROPHARMACOLOGY |
| 690 | 1 | 0 | |a NONHUMAN |
| 690 | 1 | 0 | |a PRIORITY JOURNAL |
| 690 | 1 | 0 | |a REVIEW |
| 690 | 1 | 0 | |a SIGNAL TRANSDUCTION |
| 690 | 1 | 0 | |a STRESS |
| 690 | 1 | 0 | |a ANIMALS |
| 690 | 1 | 0 | |a BRAIN |
| 690 | 1 | 0 | |a CORTICOTROPIN-RELEASING HORMONE |
| 690 | 1 | 0 | |a HUMANS |
| 690 | 1 | 0 | |a MENTAL DISORDERS |
| 690 | 1 | 0 | |a SIGNAL TRANSDUCTION |
| 690 | 1 | 0 | |a STRESS |
| 690 | 1 | 0 | |a STRESS, PHYSIOLOGICAL |
| 700 | 1 | |a Holsboer, F. | |
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