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Cellular Prion Protein (PrP(c)) and Hypoxia: True to Each Other in Good Times and in Bad, in Sickness, and in Health

The cellular prion protein (PrP(c)) and hypoxia appear to be tightly intertwined. Beneficial effects of PrP(c) on neuronal survival under hypoxic conditions such as focal cerebral ischemia are strongly supported. Conversely, increasing evidence indicates detrimental effects of increased PrP(c) expre...

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Autores principales: Ramljak, Sanja, Herlyn, Holger, Zerr, Inga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165248/
https://www.ncbi.nlm.nih.gov/pubmed/28066187
http://dx.doi.org/10.3389/fncel.2016.00292
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author Ramljak, Sanja
Herlyn, Holger
Zerr, Inga
author_facet Ramljak, Sanja
Herlyn, Holger
Zerr, Inga
author_sort Ramljak, Sanja
collection PubMed
description The cellular prion protein (PrP(c)) and hypoxia appear to be tightly intertwined. Beneficial effects of PrP(c) on neuronal survival under hypoxic conditions such as focal cerebral ischemia are strongly supported. Conversely, increasing evidence indicates detrimental effects of increased PrP(c) expression on cancer progression, another condition accompanied by low oxygen tensions. A switch between anaerobic and aerobic metabolism characterizes both conditions. A cellular process that might unite both is glycolysis. Putative role of PrP(c) in stimulation of glycolysis in times of need is indeed thought provoking. A significance of astrocytic PrP(c) expression for neuronal survival under hypoxic conditions and possible association of PrP(c) with the astrocyte-neuron lactate shuttle is considered. We posit PrP(c)-induced lactate production via transactivation of lactate dehydrogenase A by hypoxia inducible factor 1α as an important factor for survival of both neurons and tumor cells in hypoxic microenvironment. Concomitantly, we discuss a cross-talk between Wnt/β-catenin and PI3K/Akt signaling pathways in executing PrP(c)-induced activation of glycolysis. Finally, we would like to emphasize that we see a great potential in joining expertise from both fields, neuroscience and cancer research in revealing the mechanisms underlying hypoxia-related pathologies. PrP(c) may prove focal point for future research.
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spelling pubmed-51652482017-01-06 Cellular Prion Protein (PrP(c)) and Hypoxia: True to Each Other in Good Times and in Bad, in Sickness, and in Health Ramljak, Sanja Herlyn, Holger Zerr, Inga Front Cell Neurosci Neuroscience The cellular prion protein (PrP(c)) and hypoxia appear to be tightly intertwined. Beneficial effects of PrP(c) on neuronal survival under hypoxic conditions such as focal cerebral ischemia are strongly supported. Conversely, increasing evidence indicates detrimental effects of increased PrP(c) expression on cancer progression, another condition accompanied by low oxygen tensions. A switch between anaerobic and aerobic metabolism characterizes both conditions. A cellular process that might unite both is glycolysis. Putative role of PrP(c) in stimulation of glycolysis in times of need is indeed thought provoking. A significance of astrocytic PrP(c) expression for neuronal survival under hypoxic conditions and possible association of PrP(c) with the astrocyte-neuron lactate shuttle is considered. We posit PrP(c)-induced lactate production via transactivation of lactate dehydrogenase A by hypoxia inducible factor 1α as an important factor for survival of both neurons and tumor cells in hypoxic microenvironment. Concomitantly, we discuss a cross-talk between Wnt/β-catenin and PI3K/Akt signaling pathways in executing PrP(c)-induced activation of glycolysis. Finally, we would like to emphasize that we see a great potential in joining expertise from both fields, neuroscience and cancer research in revealing the mechanisms underlying hypoxia-related pathologies. PrP(c) may prove focal point for future research. Frontiers Media S.A. 2016-12-19 /pmc/articles/PMC5165248/ /pubmed/28066187 http://dx.doi.org/10.3389/fncel.2016.00292 Text en Copyright © 2016 Ramljak, Herlyn and Zerr. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Ramljak, Sanja
Herlyn, Holger
Zerr, Inga
Cellular Prion Protein (PrP(c)) and Hypoxia: True to Each Other in Good Times and in Bad, in Sickness, and in Health
title Cellular Prion Protein (PrP(c)) and Hypoxia: True to Each Other in Good Times and in Bad, in Sickness, and in Health
title_full Cellular Prion Protein (PrP(c)) and Hypoxia: True to Each Other in Good Times and in Bad, in Sickness, and in Health
title_fullStr Cellular Prion Protein (PrP(c)) and Hypoxia: True to Each Other in Good Times and in Bad, in Sickness, and in Health
title_full_unstemmed Cellular Prion Protein (PrP(c)) and Hypoxia: True to Each Other in Good Times and in Bad, in Sickness, and in Health
title_short Cellular Prion Protein (PrP(c)) and Hypoxia: True to Each Other in Good Times and in Bad, in Sickness, and in Health
title_sort cellular prion protein (prp(c)) and hypoxia: true to each other in good times and in bad, in sickness, and in health
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165248/
https://www.ncbi.nlm.nih.gov/pubmed/28066187
http://dx.doi.org/10.3389/fncel.2016.00292
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