Journal
BRAIN RESEARCH BULLETIN
Volume 151, Issue -, Pages 74-83Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2018.12.012
Keywords
Neuroprotection; P2Y(1)receptor; P2Y(13)receptor; P2X7 receptor; Oxidative stress; Genotoxic stress
Categories
Funding
- Spanish Ministerio de Economia y Competitividad (MINECO) [BFU 2014-53654-P]
- Red de Excelencia Consolider-Ingenio Spanish Ion Channel Initiative [BFU2015-70067REDC]
- Comunidad de Madrid [BRADE-CM S2013/ICE-2958]
- Fundacion Ramon Areces Grant [PR2018/16-02]
- FPU fellowship
- FPI fellowship
- Ramon y Cajal contract [RYC-2013-13290]
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Nucleotides can contribute to the survival of different glial and neuronal models at the nervous system via activation of purinergic P2X and P2Y receptors. Their activation counteracts different proapoptotic events, such as excitotoxicity, mitochondrial impairment, oxidative stress and DNA damage, which concur to elicit cell loss in different processes of neurodegeneration and brain injury. Thus, it is frequent to find that different neuroprotective mediators converge in the activation of the same intracellular survival pathways to protect cells from death. The present review focuses on the role of P2Y(1) and P2Y(13) metabotropic receptors, and P2X7 ionotropic receptors to regulate the balance between survival and apoptosis. In particular, we analyze the intracellular pathways involved in the signaling of these nucleotide receptors to elicit survival, including calcium/PLC, PI3K/Akt/GSK3, MAPK cascades, and the expression of antioxidant and antiapoptotic genes. This review emphasizes the novel contribution of nucleotide receptors to maintain cell homeostasis through the regulation of MAP kinases and phosphatases. Unraveling the different roles found for nucleotide receptors in different models and cellular contexts may be crucial to delineate future therapeutic applications based on targeting nucleotide receptors for neuroprotection.
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