The effects of painless nerve growth factor on human microglia polarization

Lisi, Lucia and Marinelli, Silvia and Ciotti, Gabriella Maria Pia and Pizzoferrato, Michela and Palmerio, Federica and Chiavari, Marta and Cattaneo, Antonino and Navarra, Pierluigi (2022) The effects of painless nerve growth factor on human microglia polarization. Frontiers in Cellular Neuroscience, 16. ISSN 1662-5102

[thumbnail of pubmed-zip/versions/1/package-entries/fncel-16-969058/fncel-16-969058.pdf] Text
pubmed-zip/versions/1/package-entries/fncel-16-969058/fncel-16-969058.pdf - Published Version

Download (5MB)

Abstract

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.

Item Type: Article
Subjects: Oalibrary Press > Medical Science
Divisions: Faculty of Law, Arts and Social Sciences > School of Humanities
Depositing User: Managing Editor
Date Deposited: 25 Mar 2023 12:43
Last Modified: 07 Mar 2024 07:56
URI: http://asian.go4publish.com/id/eprint/1739

Actions (login required)

View Item
View Item