Dual-Specificity Phosphatase Regulation in Neurons and Glial Cells



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Pérez Sen, Raquel and Queipo, María José and Gil Redondo, Juan Carlos and Ortega de la O, Felipe and Gómez Villafuertes, Rosa and Miras Portugal, María Teresa and García Delicado, Esmerilda (2019) Dual-Specificity Phosphatase Regulation in Neurons and Glial Cells. International Journal of Molecular Sciences, 20 (8). p. 1999. ISSN 1422-0067

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Official URL: https://doi.org/10.3390/ijms20081999


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.

Item Type:Article
Uncontrolled Keywords:dual-specificity phosphatases; MAP kinases; nucleotide receptors; P2X7; P2Y13; BDNF; cannabinoids; granule neurons; astrocytes
Subjects:Medical sciences > Veterinary > Microbiology
ID Code:64702
Deposited On:19 Apr 2021 15:31
Last Modified:20 Apr 2021 08:28

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