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Unravelling the mechanotransduction pathways in Alzheimer’s disease

Alzheimer’s disease (AD) represents one of the most common and debilitating neurodegenerative disorders. By the end of 2040, AD patients might reach 11.2 million in the USA, around 70% higher than 2022, with severe consequences on the society. As now, we still need research to find effective methods...

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Autores principales: Donnaloja, Francesca, Limonta, Emma, Mancosu, Christian, Morandi, Francesco, Boeri, Lucia, Albani, Diego, Raimondi, Manuela Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045049/
https://www.ncbi.nlm.nih.gov/pubmed/36978103
http://dx.doi.org/10.1186/s13036-023-00336-w
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author Donnaloja, Francesca
Limonta, Emma
Mancosu, Christian
Morandi, Francesco
Boeri, Lucia
Albani, Diego
Raimondi, Manuela Teresa
author_facet Donnaloja, Francesca
Limonta, Emma
Mancosu, Christian
Morandi, Francesco
Boeri, Lucia
Albani, Diego
Raimondi, Manuela Teresa
author_sort Donnaloja, Francesca
collection PubMed
description Alzheimer’s disease (AD) represents one of the most common and debilitating neurodegenerative disorders. By the end of 2040, AD patients might reach 11.2 million in the USA, around 70% higher than 2022, with severe consequences on the society. As now, we still need research to find effective methods to treat AD. Most studies focused on the tau and amyloid hypothesis, but many other factors are likely involved in the pathophysiology of AD. In this review, we summarize scientific evidence dealing with the mechanotransduction players in AD to highlight the most relevant mechano-responsive elements that play a role in AD pathophysiology. We focused on the AD-related role of extracellular matrix (ECM), nuclear lamina, nuclear transport and synaptic activity. The literature supports that ECM alteration causes the lamin A increment in the AD patients, leading to the formation of nuclear blebs and invaginations. Nuclear blebs have consequences on the nuclear pore complexes, impairing nucleo-cytoplasmic transport. This may result in tau hyperphosphorylation and its consequent self-aggregation in tangles, which impairs the neurotransmitters transport. It all exacerbates in synaptic transmission impairment, leading to the characteristic AD patient’s memory loss. Here we related for the first time all the evidence associating the mechanotransduction pathway with neurons. In addition, we highlighted the entire pathway influencing neurodegenerative diseases, paving the way for new research perspectives in the context of AD and related pathologies.
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spelling pubmed-100450492023-03-29 Unravelling the mechanotransduction pathways in Alzheimer’s disease Donnaloja, Francesca Limonta, Emma Mancosu, Christian Morandi, Francesco Boeri, Lucia Albani, Diego Raimondi, Manuela Teresa J Biol Eng Review Alzheimer’s disease (AD) represents one of the most common and debilitating neurodegenerative disorders. By the end of 2040, AD patients might reach 11.2 million in the USA, around 70% higher than 2022, with severe consequences on the society. As now, we still need research to find effective methods to treat AD. Most studies focused on the tau and amyloid hypothesis, but many other factors are likely involved in the pathophysiology of AD. In this review, we summarize scientific evidence dealing with the mechanotransduction players in AD to highlight the most relevant mechano-responsive elements that play a role in AD pathophysiology. We focused on the AD-related role of extracellular matrix (ECM), nuclear lamina, nuclear transport and synaptic activity. The literature supports that ECM alteration causes the lamin A increment in the AD patients, leading to the formation of nuclear blebs and invaginations. Nuclear blebs have consequences on the nuclear pore complexes, impairing nucleo-cytoplasmic transport. This may result in tau hyperphosphorylation and its consequent self-aggregation in tangles, which impairs the neurotransmitters transport. It all exacerbates in synaptic transmission impairment, leading to the characteristic AD patient’s memory loss. Here we related for the first time all the evidence associating the mechanotransduction pathway with neurons. In addition, we highlighted the entire pathway influencing neurodegenerative diseases, paving the way for new research perspectives in the context of AD and related pathologies. BioMed Central 2023-03-28 /pmc/articles/PMC10045049/ /pubmed/36978103 http://dx.doi.org/10.1186/s13036-023-00336-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Donnaloja, Francesca
Limonta, Emma
Mancosu, Christian
Morandi, Francesco
Boeri, Lucia
Albani, Diego
Raimondi, Manuela Teresa
Unravelling the mechanotransduction pathways in Alzheimer’s disease
title Unravelling the mechanotransduction pathways in Alzheimer’s disease
title_full Unravelling the mechanotransduction pathways in Alzheimer’s disease
title_fullStr Unravelling the mechanotransduction pathways in Alzheimer’s disease
title_full_unstemmed Unravelling the mechanotransduction pathways in Alzheimer’s disease
title_short Unravelling the mechanotransduction pathways in Alzheimer’s disease
title_sort unravelling the mechanotransduction pathways in alzheimer’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045049/
https://www.ncbi.nlm.nih.gov/pubmed/36978103
http://dx.doi.org/10.1186/s13036-023-00336-w
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