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Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies

Alzheimer’s disease (AD) is arguably the most common cause of dementia in the elderly and is marked by progressive synaptic degeneration, which in turn leads to cognitive decline. Studies in patients and in various AD models have shown that one of the early signatures of AD is neuronal hyperactivity...

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Autores principales: Ghatak, Swagata, Nakamura, Tomohiro, Lipton, Stuart A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932935/
https://www.ncbi.nlm.nih.gov/pubmed/36817649
http://dx.doi.org/10.3389/fncir.2023.1099467
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author Ghatak, Swagata
Nakamura, Tomohiro
Lipton, Stuart A.
author_facet Ghatak, Swagata
Nakamura, Tomohiro
Lipton, Stuart A.
author_sort Ghatak, Swagata
collection PubMed
description Alzheimer’s disease (AD) is arguably the most common cause of dementia in the elderly and is marked by progressive synaptic degeneration, which in turn leads to cognitive decline. Studies in patients and in various AD models have shown that one of the early signatures of AD is neuronal hyperactivity. This excessive electrical activity contributes to dysregulated neural network function and synaptic damage. Mechanistically, evidence suggests that hyperexcitability accelerates production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that contribute to neural network impairment and synapse loss. This review focuses on the pathways and molecular changes that cause hyperexcitability and how RNS-dependent posttranslational modifications, represented predominantly by protein S-nitrosylation, mediate, at least in part, the deleterious effects of hyperexcitability on single neurons and the neural network, resulting in synaptic loss in AD.
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spelling pubmed-99329352023-02-17 Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies Ghatak, Swagata Nakamura, Tomohiro Lipton, Stuart A. Front Neural Circuits Neural Circuits Alzheimer’s disease (AD) is arguably the most common cause of dementia in the elderly and is marked by progressive synaptic degeneration, which in turn leads to cognitive decline. Studies in patients and in various AD models have shown that one of the early signatures of AD is neuronal hyperactivity. This excessive electrical activity contributes to dysregulated neural network function and synaptic damage. Mechanistically, evidence suggests that hyperexcitability accelerates production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that contribute to neural network impairment and synapse loss. This review focuses on the pathways and molecular changes that cause hyperexcitability and how RNS-dependent posttranslational modifications, represented predominantly by protein S-nitrosylation, mediate, at least in part, the deleterious effects of hyperexcitability on single neurons and the neural network, resulting in synaptic loss in AD. Frontiers Media S.A. 2023-02-02 /pmc/articles/PMC9932935/ /pubmed/36817649 http://dx.doi.org/10.3389/fncir.2023.1099467 Text en Copyright © 2023 Ghatak, Nakamura and Lipton. 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 Neural Circuits
Ghatak, Swagata
Nakamura, Tomohiro
Lipton, Stuart A.
Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies
title Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies
title_full Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies
title_fullStr Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies
title_full_unstemmed Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies
title_short Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies
title_sort aberrant protein s-nitrosylation contributes to hyperexcitability-induced synaptic damage in alzheimer’s disease: mechanistic insights and potential therapies
topic Neural Circuits
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932935/
https://www.ncbi.nlm.nih.gov/pubmed/36817649
http://dx.doi.org/10.3389/fncir.2023.1099467
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