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Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence

Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogeno...

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Autores principales: Colizzi, Marco, Bortoletto, Riccardo, Colli, Chiara, Bonomo, Enrico, Pagliaro, Daniele, Maso, Elisa, Di Gennaro, Gianfranco, Balestrieri, Matteo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9650099/
https://www.ncbi.nlm.nih.gov/pubmed/36387000
http://dx.doi.org/10.3389/fpsyt.2022.1038122
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author Colizzi, Marco
Bortoletto, Riccardo
Colli, Chiara
Bonomo, Enrico
Pagliaro, Daniele
Maso, Elisa
Di Gennaro, Gianfranco
Balestrieri, Matteo
author_facet Colizzi, Marco
Bortoletto, Riccardo
Colli, Chiara
Bonomo, Enrico
Pagliaro, Daniele
Maso, Elisa
Di Gennaro, Gianfranco
Balestrieri, Matteo
author_sort Colizzi, Marco
collection PubMed
description Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogenous attempt to contrast such neurodegeneration-related pathophysiological mechanisms, restore homeostatic balance, and prevent further damage. Among these naturally occurring molecules, palmitoylethanolamide (PEA) has been independently associated with neuroprotective and anti-inflammatory properties, raising interest into the possibility that its supplementation might represent a novel therapeutic approach in supporting the body-own regulation of many pathophysiological processes potentially contributing to neurocognitive disorders. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in neurocognitive disorders, finding 33 eligible outputs. Studies conducted in animal models of neurodegeneration indicate that PEA improves neurobehavioral functions, including memory and learning, by reducing oxidative stress and pro-inflammatory and astrocyte marker expression as well as rebalancing glutamatergic transmission. PEA was found to promote neurogenesis, especially in the hippocampus, neuronal viability and survival, and microtubule-associated protein 2 and brain-derived neurotrophic factor expression, while inhibiting mast cell infiltration/degranulation and astrocyte activation. It also demonstrated to mitigate β-amyloid-induced astrogliosis, by modulating lipid peroxidation, protein nytrosylation, inducible nitric oxide synthase induction, reactive oxygen species production, caspase3 activation, amyloidogenesis, and tau protein hyperphosphorylation. Such effects were related to PEA ability to indirectly activate cannabinoid receptors and modulate proliferator-activated receptor-α (PPAR-α) activity. Importantly, preclinical evidence suggests that PEA may act as a disease-modifying-drug in the early stage of a neurocognitive disorder, while its protective effect in the frank disorder may be less relevant. Limited human research suggests that PEA supplementation reduces fatigue and cognitive impairment, the latter being also meta-analytically confirmed in 3 eligible studies. PEA improved global executive function, working memory, language deficits, daily living activities, possibly by modulating cortical oscillatory activity and GABAergic transmission. There is currently no established cure for neurocognitive disorders but only treatments to temporarily reduce symptom severity. In the search for compounds able to protect against the pathophysiological mechanisms leading to neurocognitive disorders, PEA may represent a valid therapeutic option to prevent neurodegeneration and support endogenous repair processes against disease progression.
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spelling pubmed-96500992022-11-15 Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence Colizzi, Marco Bortoletto, Riccardo Colli, Chiara Bonomo, Enrico Pagliaro, Daniele Maso, Elisa Di Gennaro, Gianfranco Balestrieri, Matteo Front Psychiatry Psychiatry Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogenous attempt to contrast such neurodegeneration-related pathophysiological mechanisms, restore homeostatic balance, and prevent further damage. Among these naturally occurring molecules, palmitoylethanolamide (PEA) has been independently associated with neuroprotective and anti-inflammatory properties, raising interest into the possibility that its supplementation might represent a novel therapeutic approach in supporting the body-own regulation of many pathophysiological processes potentially contributing to neurocognitive disorders. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in neurocognitive disorders, finding 33 eligible outputs. Studies conducted in animal models of neurodegeneration indicate that PEA improves neurobehavioral functions, including memory and learning, by reducing oxidative stress and pro-inflammatory and astrocyte marker expression as well as rebalancing glutamatergic transmission. PEA was found to promote neurogenesis, especially in the hippocampus, neuronal viability and survival, and microtubule-associated protein 2 and brain-derived neurotrophic factor expression, while inhibiting mast cell infiltration/degranulation and astrocyte activation. It also demonstrated to mitigate β-amyloid-induced astrogliosis, by modulating lipid peroxidation, protein nytrosylation, inducible nitric oxide synthase induction, reactive oxygen species production, caspase3 activation, amyloidogenesis, and tau protein hyperphosphorylation. Such effects were related to PEA ability to indirectly activate cannabinoid receptors and modulate proliferator-activated receptor-α (PPAR-α) activity. Importantly, preclinical evidence suggests that PEA may act as a disease-modifying-drug in the early stage of a neurocognitive disorder, while its protective effect in the frank disorder may be less relevant. Limited human research suggests that PEA supplementation reduces fatigue and cognitive impairment, the latter being also meta-analytically confirmed in 3 eligible studies. PEA improved global executive function, working memory, language deficits, daily living activities, possibly by modulating cortical oscillatory activity and GABAergic transmission. There is currently no established cure for neurocognitive disorders but only treatments to temporarily reduce symptom severity. In the search for compounds able to protect against the pathophysiological mechanisms leading to neurocognitive disorders, PEA may represent a valid therapeutic option to prevent neurodegeneration and support endogenous repair processes against disease progression. Frontiers Media S.A. 2022-10-28 /pmc/articles/PMC9650099/ /pubmed/36387000 http://dx.doi.org/10.3389/fpsyt.2022.1038122 Text en Copyright © 2022 Colizzi, Bortoletto, Colli, Bonomo, Pagliaro, Maso, Di Gennaro and Balestrieri. 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 Psychiatry
Colizzi, Marco
Bortoletto, Riccardo
Colli, Chiara
Bonomo, Enrico
Pagliaro, Daniele
Maso, Elisa
Di Gennaro, Gianfranco
Balestrieri, Matteo
Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence
title Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence
title_full Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence
title_fullStr Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence
title_full_unstemmed Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence
title_short Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence
title_sort therapeutic effect of palmitoylethanolamide in cognitive decline: a systematic review and preliminary meta-analysis of preclinical and clinical evidence
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9650099/
https://www.ncbi.nlm.nih.gov/pubmed/36387000
http://dx.doi.org/10.3389/fpsyt.2022.1038122
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