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The effects of painless nerve growth factor on human microglia polarization
Previous studies in the rat suggest that microglial cells represent a potential druggable target for nerve growth factor (NGF) in the brain. The painless human Nerve Growth Factor (hNGFp) is a recombinant mutated form of human nerve growth factor (hNGF) that shows identical neurotrophic and neuropro...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9633670/ https://www.ncbi.nlm.nih.gov/pubmed/36339818 http://dx.doi.org/10.3389/fncel.2022.969058 |
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author | Lisi, Lucia Marinelli, Silvia Ciotti, Gabriella Maria Pia Pizzoferrato, Michela Palmerio, Federica Chiavari, Marta Cattaneo, Antonino Navarra, Pierluigi |
author_facet | Lisi, Lucia Marinelli, Silvia Ciotti, Gabriella Maria Pia Pizzoferrato, Michela Palmerio, Federica Chiavari, Marta Cattaneo, Antonino Navarra, Pierluigi |
author_sort | Lisi, Lucia |
collection | PubMed |
description | Previous studies in the rat suggest that microglial cells represent a potential druggable target for nerve growth factor (NGF) in the brain. The painless human Nerve Growth Factor (hNGFp) is a recombinant mutated form of human nerve growth factor (hNGF) that shows identical neurotrophic and neuroprotective properties of wild-type NGF but displays at least 10-fold lower algogenic activity. From the pharmacological point of view, hNGFp is a biased tropomyosin receptor kinase A (TrkA) agonist and displays a significantly lower affinity for the p75 neurotrophin receptor (p75NTR). This study aimed to evaluate the expression of TrkA and p75NTR NGF receptors in two different human microglia cell lines, and to investigate the effects of hNGFp and wild-type NGF (NGF) on L-arginine metabolism, taken as a marker of microglia polarization. Both NGF receptors are expressed in human microglia cell lines and are effective in transducing signals triggered by NGF and hNGFp. The latter and, to a lesser extent, NGF inhibit cytokine-stimulated inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in these cells. Conversely NGF but not hNGFp stimulates arginase-mediated urea production. |
format | Online Article Text |
id | pubmed-9633670 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96336702022-11-05 The effects of painless nerve growth factor on human microglia polarization Lisi, Lucia Marinelli, Silvia Ciotti, Gabriella Maria Pia Pizzoferrato, Michela Palmerio, Federica Chiavari, Marta Cattaneo, Antonino Navarra, Pierluigi Front Cell Neurosci Neuroscience Previous studies in the rat suggest that microglial cells represent a potential druggable target for nerve growth factor (NGF) in the brain. The painless human Nerve Growth Factor (hNGFp) is a recombinant mutated form of human nerve growth factor (hNGF) that shows identical neurotrophic and neuroprotective properties of wild-type NGF but displays at least 10-fold lower algogenic activity. From the pharmacological point of view, hNGFp is a biased tropomyosin receptor kinase A (TrkA) agonist and displays a significantly lower affinity for the p75 neurotrophin receptor (p75NTR). This study aimed to evaluate the expression of TrkA and p75NTR NGF receptors in two different human microglia cell lines, and to investigate the effects of hNGFp and wild-type NGF (NGF) on L-arginine metabolism, taken as a marker of microglia polarization. Both NGF receptors are expressed in human microglia cell lines and are effective in transducing signals triggered by NGF and hNGFp. The latter and, to a lesser extent, NGF inhibit cytokine-stimulated inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in these cells. Conversely NGF but not hNGFp stimulates arginase-mediated urea production. Frontiers Media S.A. 2022-10-21 /pmc/articles/PMC9633670/ /pubmed/36339818 http://dx.doi.org/10.3389/fncel.2022.969058 Text en Copyright © 2022 Lisi, Marinelli, Ciotti, Pizzoferrato, Palmerio, Chiavari, Cattaneo and Navarra. https://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) and the copyright owner(s) 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 Lisi, Lucia Marinelli, Silvia Ciotti, Gabriella Maria Pia Pizzoferrato, Michela Palmerio, Federica Chiavari, Marta Cattaneo, Antonino Navarra, Pierluigi The effects of painless nerve growth factor on human microglia polarization |
title | The effects of painless nerve growth factor on human microglia polarization |
title_full | The effects of painless nerve growth factor on human microglia polarization |
title_fullStr | The effects of painless nerve growth factor on human microglia polarization |
title_full_unstemmed | The effects of painless nerve growth factor on human microglia polarization |
title_short | The effects of painless nerve growth factor on human microglia polarization |
title_sort | effects of painless nerve growth factor on human microglia polarization |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9633670/ https://www.ncbi.nlm.nih.gov/pubmed/36339818 http://dx.doi.org/10.3389/fncel.2022.969058 |
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