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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.754502/full |
| _version_ | 1818856428111134720 |
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| author | Luigi Manni Giorgio Conti Antonio Chiaretti Marzia Soligo |
| author_facet | Luigi Manni Giorgio Conti Antonio Chiaretti Marzia Soligo |
| author_sort | Luigi Manni |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T08:24:20Z |
| format | Article |
| id | doaj.art-c61e5f160f2b4259aaf62ed2afadf5df |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T08:24:20Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-c61e5f160f2b4259aaf62ed2afadf5df2022-12-21T20:29:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-11-011210.3389/fphar.2021.754502754502Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and NeurotraumaLuigi Manni0Giorgio Conti1Antonio Chiaretti2Marzia Soligo3Institute of Translational Pharmacology, National Research Council of Italy (CNR), Rome, ItalyDepartment of Emergency, Intensive Pediatric Therapy and Pediatric Trauma Center, Anesthesiological and Reanimation Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, ItalyDepartment of Woman and Child Health, Institute of Pediatrics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, ItalyInstitute of Translational Pharmacology, National Research Council of Italy (CNR), Rome, ItalySince 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.754502/fullnerve growth factorintranasal deliverypharmacologyneurodegenerationneurotrauma and neurodegenerative disease |
| spellingShingle | Luigi Manni Giorgio Conti Antonio Chiaretti Marzia Soligo Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma Frontiers in Pharmacology nerve growth factor intranasal delivery pharmacology neurodegeneration neurotrauma and neurodegenerative disease |
| 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 | nerve growth factor intranasal delivery pharmacology neurodegeneration neurotrauma and neurodegenerative disease |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.754502/full |
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