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Small Endogenous Ligands Modulation of Nerve Growth Factor Bioactivity: A Structural Biology Overview
Experiments with cell cultures and animal models have provided solid support for the assumption that Nerve Growth Factor (NGF) plays a key role in the regulation of neuronal cell survival and death. Recently, endogenous ligands have been proposed as physiological modulators of NGF biological activit...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700322/ https://www.ncbi.nlm.nih.gov/pubmed/34943971 http://dx.doi.org/10.3390/cells10123462 |
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author | Paoletti, Francesca Lamba, Doriano |
author_facet | Paoletti, Francesca Lamba, Doriano |
author_sort | Paoletti, Francesca |
collection | PubMed |
description | Experiments with cell cultures and animal models have provided solid support for the assumption that Nerve Growth Factor (NGF) plays a key role in the regulation of neuronal cell survival and death. Recently, endogenous ligands have been proposed as physiological modulators of NGF biological activity as part of this regulatory cascade. However, the structural and mechanistic determinants for NGF bioactivity remain to be elucidated. We recently unveiled, by an integrated structural biology approach, the ATP binding sites of NGF and investigated the effects on TrkA and p75(NTR) receptors binding. These results pinpoint ATP as a genuine endogenous modulator of NGF signaling, paving the way to the characterization of not-yet-identified chemical diverse endogenous biological active small molecules as novel modulators of NGF. The present review aims at providing an overview of the currently available 3D structures of NGF in complex with different small endogenous ligands, featuring the molecular footprints of the small molecules binding. This knowledge is essential for further understanding the functional role of small endogenous ligands in the modulation of neurotrophins signaling in physiological and pathological conditions and for better exploiting the therapeutic potentialities of NGF. |
format | Online Article Text |
id | pubmed-8700322 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87003222021-12-24 Small Endogenous Ligands Modulation of Nerve Growth Factor Bioactivity: A Structural Biology Overview Paoletti, Francesca Lamba, Doriano Cells Review Experiments with cell cultures and animal models have provided solid support for the assumption that Nerve Growth Factor (NGF) plays a key role in the regulation of neuronal cell survival and death. Recently, endogenous ligands have been proposed as physiological modulators of NGF biological activity as part of this regulatory cascade. However, the structural and mechanistic determinants for NGF bioactivity remain to be elucidated. We recently unveiled, by an integrated structural biology approach, the ATP binding sites of NGF and investigated the effects on TrkA and p75(NTR) receptors binding. These results pinpoint ATP as a genuine endogenous modulator of NGF signaling, paving the way to the characterization of not-yet-identified chemical diverse endogenous biological active small molecules as novel modulators of NGF. The present review aims at providing an overview of the currently available 3D structures of NGF in complex with different small endogenous ligands, featuring the molecular footprints of the small molecules binding. This knowledge is essential for further understanding the functional role of small endogenous ligands in the modulation of neurotrophins signaling in physiological and pathological conditions and for better exploiting the therapeutic potentialities of NGF. MDPI 2021-12-08 /pmc/articles/PMC8700322/ /pubmed/34943971 http://dx.doi.org/10.3390/cells10123462 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Paoletti, Francesca Lamba, Doriano Small Endogenous Ligands Modulation of Nerve Growth Factor Bioactivity: A Structural Biology Overview |
title | Small Endogenous Ligands Modulation of Nerve Growth Factor Bioactivity: A Structural Biology Overview |
title_full | Small Endogenous Ligands Modulation of Nerve Growth Factor Bioactivity: A Structural Biology Overview |
title_fullStr | Small Endogenous Ligands Modulation of Nerve Growth Factor Bioactivity: A Structural Biology Overview |
title_full_unstemmed | Small Endogenous Ligands Modulation of Nerve Growth Factor Bioactivity: A Structural Biology Overview |
title_short | Small Endogenous Ligands Modulation of Nerve Growth Factor Bioactivity: A Structural Biology Overview |
title_sort | small endogenous ligands modulation of nerve growth factor bioactivity: a structural biology overview |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700322/ https://www.ncbi.nlm.nih.gov/pubmed/34943971 http://dx.doi.org/10.3390/cells10123462 |
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