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Signalling Pathways Implicated in Alzheimer′s Disease Neurodegeneration in Individuals with and without Down Syndrome

Down syndrome (DS), the most common cause of intellectual disability of genetic origin, is characterized by alterations in central nervous system morphology and function that appear from early prenatal stages. However, by the fourth decade of life, all individuals with DS develop neuropathology iden...

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Autores principales: Martínez-Cué, Carmen, Rueda, Noemí
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555886/
https://www.ncbi.nlm.nih.gov/pubmed/32962300
http://dx.doi.org/10.3390/ijms21186906
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author Martínez-Cué, Carmen
Rueda, Noemí
author_facet Martínez-Cué, Carmen
Rueda, Noemí
author_sort Martínez-Cué, Carmen
collection PubMed
description Down syndrome (DS), the most common cause of intellectual disability of genetic origin, is characterized by alterations in central nervous system morphology and function that appear from early prenatal stages. However, by the fourth decade of life, all individuals with DS develop neuropathology identical to that found in sporadic Alzheimer’s disease (AD), including the development of amyloid plaques and neurofibrillary tangles due to hyperphosphorylation of tau protein, loss of neurons and synapses, reduced neurogenesis, enhanced oxidative stress, and mitochondrial dysfunction and neuroinflammation. It has been proposed that DS could be a useful model for studying the etiopathology of AD and to search for therapeutic targets. There is increasing evidence that the neuropathological events associated with AD are interrelated and that many of them not only are implicated in the onset of this pathology but are also a consequence of other alterations. Thus, a feedback mechanism exists between them. In this review, we summarize the signalling pathways implicated in each of the main neuropathological aspects of AD in individuals with and without DS as well as the interrelation of these pathways.
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spelling pubmed-75558862020-10-19 Signalling Pathways Implicated in Alzheimer′s Disease Neurodegeneration in Individuals with and without Down Syndrome Martínez-Cué, Carmen Rueda, Noemí Int J Mol Sci Review Down syndrome (DS), the most common cause of intellectual disability of genetic origin, is characterized by alterations in central nervous system morphology and function that appear from early prenatal stages. However, by the fourth decade of life, all individuals with DS develop neuropathology identical to that found in sporadic Alzheimer’s disease (AD), including the development of amyloid plaques and neurofibrillary tangles due to hyperphosphorylation of tau protein, loss of neurons and synapses, reduced neurogenesis, enhanced oxidative stress, and mitochondrial dysfunction and neuroinflammation. It has been proposed that DS could be a useful model for studying the etiopathology of AD and to search for therapeutic targets. There is increasing evidence that the neuropathological events associated with AD are interrelated and that many of them not only are implicated in the onset of this pathology but are also a consequence of other alterations. Thus, a feedback mechanism exists between them. In this review, we summarize the signalling pathways implicated in each of the main neuropathological aspects of AD in individuals with and without DS as well as the interrelation of these pathways. MDPI 2020-09-20 /pmc/articles/PMC7555886/ /pubmed/32962300 http://dx.doi.org/10.3390/ijms21186906 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Martínez-Cué, Carmen
Rueda, Noemí
Signalling Pathways Implicated in Alzheimer′s Disease Neurodegeneration in Individuals with and without Down Syndrome
title Signalling Pathways Implicated in Alzheimer′s Disease Neurodegeneration in Individuals with and without Down Syndrome
title_full Signalling Pathways Implicated in Alzheimer′s Disease Neurodegeneration in Individuals with and without Down Syndrome
title_fullStr Signalling Pathways Implicated in Alzheimer′s Disease Neurodegeneration in Individuals with and without Down Syndrome
title_full_unstemmed Signalling Pathways Implicated in Alzheimer′s Disease Neurodegeneration in Individuals with and without Down Syndrome
title_short Signalling Pathways Implicated in Alzheimer′s Disease Neurodegeneration in Individuals with and without Down Syndrome
title_sort signalling pathways implicated in alzheimer′s disease neurodegeneration in individuals with and without down syndrome
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555886/
https://www.ncbi.nlm.nih.gov/pubmed/32962300
http://dx.doi.org/10.3390/ijms21186906
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