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(Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis

Beside its widely studied role in the pathogenesis of Alzheimer's disease (AD), β-amyloid (Aβ) is a normal and soluble product of neuronal metabolism that regulates several key physiological functions, exerting neuromodulatory effects on synaptic plasticity, memory, and neurotransmitter release...

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Autores principales: Fagiani, Francesca, Lanni, Cristina, Racchi, Marco, Govoni, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943918/
https://www.ncbi.nlm.nih.gov/pubmed/33716668
http://dx.doi.org/10.3389/fnmol.2021.635880
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author Fagiani, Francesca
Lanni, Cristina
Racchi, Marco
Govoni, Stefano
author_facet Fagiani, Francesca
Lanni, Cristina
Racchi, Marco
Govoni, Stefano
author_sort Fagiani, Francesca
collection PubMed
description Beside its widely studied role in the pathogenesis of Alzheimer's disease (AD), β-amyloid (Aβ) is a normal and soluble product of neuronal metabolism that regulates several key physiological functions, exerting neuromodulatory effects on synaptic plasticity, memory, and neurotransmitter release. Such effects have been observed to occur in a hormetic fashion, with Aβ exhibiting a dual role influenced by its concentration, the different isoforms, or aggregation forms of the peptide. However, to date, our knowledge about the physiological functions of Aβ and, in particular, its modulatory role on synaptic activity and neurotransmission in the normal brain is fragmentary, thus hindering a clear comprehension of the biological mechanisms underlying the derangement from function to dysfunction. In particular, according to the amyloid cascade hypothesis, the switch from physiology to pathology is linked to the abnormal increase in Aβ levels, due to an imbalance in Aβ production and clearance. In this regard, increased Aβ levels have been hypothesized to induce early defects in synaptic function and such alterations have been suggested to account, at least in part, for the onset of neuropsychiatric symptoms (e.g., apathy, anxiety, changes in mood, depression, and agitation/aggression), frequently observed in the prodromal stage of AD. Therefore, understanding the biological mechanisms underlying early synaptic alterations in AD is a key starting point to frame the relevant time windows for AD treatment and to gain insight into AD etiopathogenesis.
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spelling pubmed-79439182021-03-11 (Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis Fagiani, Francesca Lanni, Cristina Racchi, Marco Govoni, Stefano Front Mol Neurosci Neuroscience Beside its widely studied role in the pathogenesis of Alzheimer's disease (AD), β-amyloid (Aβ) is a normal and soluble product of neuronal metabolism that regulates several key physiological functions, exerting neuromodulatory effects on synaptic plasticity, memory, and neurotransmitter release. Such effects have been observed to occur in a hormetic fashion, with Aβ exhibiting a dual role influenced by its concentration, the different isoforms, or aggregation forms of the peptide. However, to date, our knowledge about the physiological functions of Aβ and, in particular, its modulatory role on synaptic activity and neurotransmission in the normal brain is fragmentary, thus hindering a clear comprehension of the biological mechanisms underlying the derangement from function to dysfunction. In particular, according to the amyloid cascade hypothesis, the switch from physiology to pathology is linked to the abnormal increase in Aβ levels, due to an imbalance in Aβ production and clearance. In this regard, increased Aβ levels have been hypothesized to induce early defects in synaptic function and such alterations have been suggested to account, at least in part, for the onset of neuropsychiatric symptoms (e.g., apathy, anxiety, changes in mood, depression, and agitation/aggression), frequently observed in the prodromal stage of AD. Therefore, understanding the biological mechanisms underlying early synaptic alterations in AD is a key starting point to frame the relevant time windows for AD treatment and to gain insight into AD etiopathogenesis. Frontiers Media S.A. 2021-02-24 /pmc/articles/PMC7943918/ /pubmed/33716668 http://dx.doi.org/10.3389/fnmol.2021.635880 Text en Copyright © 2021 Fagiani, Lanni, Racchi and Govoni. http://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 Neuroscience
Fagiani, Francesca
Lanni, Cristina
Racchi, Marco
Govoni, Stefano
(Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis
title (Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis
title_full (Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis
title_fullStr (Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis
title_full_unstemmed (Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis
title_short (Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis
title_sort (dys)regulation of synaptic activity and neurotransmitter release by β-amyloid: a look beyond alzheimer's disease pathogenesis
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943918/
https://www.ncbi.nlm.nih.gov/pubmed/33716668
http://dx.doi.org/10.3389/fnmol.2021.635880
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