Neuroprotection Mediated by P2Y13 Nucleotide Receptors in Neurons

Computational and Structural Biotechnology Journal
Raquel Pérez-SenM Teresa Miras-Portugal

Abstract

ADP-specific P2Y13 receptor constitutes one of the most recently identified nucleotide receptor and the understanding of their physiological role is currently under investigation. Cerebellar astrocytes and granule neurons provide excellent models to study P2Y13 expression and function since the first identification of ADP-evoked calcium responses not attributable to the related P2Y1 receptor was performed in these cell populations. In this regard, all responses induced by ADP analogues in astrocytes resulted to be Gi-coupled activities mediated by P2Y13 instead of P2Y1 receptors. Similarly, both glycogen synthase kinase-3 (GSK3) and ERK1/2 signaling triggered by 2MeSADP in cerebellar granule neurons were also dependent on Gi-coupled receptors, and mediated by PI3K activity. In granule neurons, P2Y13 receptor was specifically coupled to the main neuronal survival PI3K/Akt-cascade targeting GSK3 phosphorylation. GSK3 inhibition led to nuclear translocation of transcriptional targets, including β-catenin and Nrf2. The activation of the Nrf2/heme oxygenase-1 (HO-1) axis was responsible for the prosurvival effect against oxidative stress. In addition, P2Y13-mediated ERK1/2 signaling in granule neurons also triggered activation of tr...Continue Reading

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Citations

Nov 1, 2015·Neuropharmacology·Ivar von Kügelgen, Kristina Hoffmann
Sep 20, 2015·Neuropharmacology·Edward BeamerBeáta Sperlágh
Sep 12, 2015·Neuropharmacology·M Teresa Miras-PortugalRaquel Perez-Sen
Apr 26, 2019·International Journal of Molecular Sciences·Raquel Pérez-SenEsmerilda G Delicado
Feb 11, 2020·British Journal of Pharmacology·Kenneth A JacobsonChrista E Müller
Mar 27, 2018·Molecular Neurobiology·Luana de Almeida-PereiraLucianne Fragel-Madeira
Oct 11, 2017·Frontiers in Pharmacology·Geoffrey Burnstock
Jun 17, 2020·Molecular Imaging·Hamideh Zarrinmayeh, Paul R Territo

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Methods Mentioned

BETA
nuclear translocation
ubiquitination
GTPase

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