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Dual-Specificity Phosphatase Regulation in Neurons and Glial Cells

Departamento de Bioquímica y Biología Molecular, Facultad de Veterinaria, Instituto Universitario de Investigación en Neuroquímica (IUIN), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdiSSC), Universidad Complutense Madrid, 28040 Madrid, Spain
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(8), 1999;
Received: 28 March 2019 / Revised: 19 April 2019 / Accepted: 19 April 2019 / Published: 23 April 2019
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Dual-specificity protein phosphatases comprise a protein phosphatase subfamily with selectivity towards mitogen-activated protein (MAP) kinases, also named MKPs, or mitogen-activated protein kinase (MAPK) phosphatases. As powerful regulators of the intensity and duration of MAPK signaling, a relevant role is envisioned for dual-specificity protein phosphatases (DUSPs) in the regulation of biological processes in the nervous system, such as differentiation, synaptic plasticity, and survival. Important neural mediators include nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) that contribute to DUSP transcriptional induction and post-translational mechanisms of DUSP protein stabilization to maintain neuronal survival and differentiation. Potent DUSP gene inducers also include cannabinoids, which preserve DUSP activity in inflammatory conditions. Additionally, nucleotides activating P2X7 and P2Y13 nucleotide receptors behave as novel players in the regulation of DUSP function. They increase cell survival in stressful conditions, regulating DUSP protein turnover and inducing DUSP gene expression. In general terms, in the context of neural cells exposed to damaging conditions, the recovery of DUSP activity is neuroprotective and counteracts pro-apoptotic over-activation of p38 and JNK. In addition, remarkable changes in DUSP function take place during the onset of neuropathologies. The restoration of proper DUSP levels and recovery of MAPK homeostasis underlie the therapeutic effect, indicating that DUSPs can be relevant targets for brain diseases. View Full-Text
Keywords: dual-specificity phosphatases; MAP kinases; nucleotide receptors; P2X7; P2Y13; BDNF; cannabinoids; granule neurons; astrocytes dual-specificity phosphatases; MAP kinases; nucleotide receptors; P2X7; P2Y13; BDNF; cannabinoids; granule neurons; astrocytes

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Pérez-Sen, R.; Queipo, M.J.; Gil-Redondo, J.C.; Ortega, F.; Gómez-Villafuertes, R.; Miras-Portugal, M.T.; Delicado, E.G. Dual-Specificity Phosphatase Regulation in Neurons and Glial Cells. Int. J. Mol. Sci. 2019, 20, 1999.

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