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Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma
Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer’s disease (AD). This hypothesis was based on the rescuing effect of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromis...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635100/ https://www.ncbi.nlm.nih.gov/pubmed/34867367 http://dx.doi.org/10.3389/fphar.2021.754502 |
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author | Manni, Luigi Conti, Giorgio Chiaretti, Antonio Soligo, Marzia |
author_facet | Manni, Luigi Conti, Giorgio Chiaretti, Antonio Soligo, Marzia |
author_sort | Manni, Luigi |
collection | PubMed |
description | Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer’s disease (AD). This hypothesis was based on the rescuing effect of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromised during the development of AD. Subsequently, the use of NGF was put forward to treat a broader spectrum of neurological conditions affecting the central nervous system, such as Parkinson’s disease, degenerative retinopathies, severe brain traumas and neurodevelopmental dysfunctions. While supported by solid rational assumptions, the progress of a pharmacology founded on these hypotheses has been hampered by the difficulty of conveying NGF towards the brain parenchyma without resorting to invasive and risky delivery methods. At the end of the last century, it was shown that NGF administered intranasally to the olfactory epithelium was able to spread into the brain parenchyma. Notably, after such delivery, pharmacologically relevant concentration of exogenous NGF was found in brain areas located at considerable distances from the injection site along the rostral-caudal axis. These observations paved the way for preclinical characterization and clinical trials on the efficacy of intranasal NGF for the treatment of neurodegenerative diseases and of the consequences of brain trauma. In this review, a summary of the preclinical and clinical studies published to date will be attempted, as well as a discussion about the mechanisms underlying the efficacy and the possible development of the pharmacology based on intranasal conveyance of NGF to the brain. |
format | Online Article Text |
id | pubmed-8635100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86351002021-12-02 Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma Manni, Luigi Conti, Giorgio Chiaretti, Antonio Soligo, Marzia Front Pharmacol Pharmacology Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer’s disease (AD). This hypothesis was based on the rescuing effect of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromised during the development of AD. Subsequently, the use of NGF was put forward to treat a broader spectrum of neurological conditions affecting the central nervous system, such as Parkinson’s disease, degenerative retinopathies, severe brain traumas and neurodevelopmental dysfunctions. While supported by solid rational assumptions, the progress of a pharmacology founded on these hypotheses has been hampered by the difficulty of conveying NGF towards the brain parenchyma without resorting to invasive and risky delivery methods. At the end of the last century, it was shown that NGF administered intranasally to the olfactory epithelium was able to spread into the brain parenchyma. Notably, after such delivery, pharmacologically relevant concentration of exogenous NGF was found in brain areas located at considerable distances from the injection site along the rostral-caudal axis. These observations paved the way for preclinical characterization and clinical trials on the efficacy of intranasal NGF for the treatment of neurodegenerative diseases and of the consequences of brain trauma. In this review, a summary of the preclinical and clinical studies published to date will be attempted, as well as a discussion about the mechanisms underlying the efficacy and the possible development of the pharmacology based on intranasal conveyance of NGF to the brain. Frontiers Media S.A. 2021-11-16 /pmc/articles/PMC8635100/ /pubmed/34867367 http://dx.doi.org/10.3389/fphar.2021.754502 Text en Copyright © 2021 Manni, Conti, Chiaretti and Soligo. 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 | Pharmacology Manni, Luigi Conti, Giorgio Chiaretti, Antonio Soligo, Marzia Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma |
title | Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma |
title_full | Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma |
title_fullStr | Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma |
title_full_unstemmed | Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma |
title_short | Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma |
title_sort | intranasal delivery of nerve growth factor in neurodegenerative diseases and neurotrauma |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635100/ https://www.ncbi.nlm.nih.gov/pubmed/34867367 http://dx.doi.org/10.3389/fphar.2021.754502 |
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