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Cellular Regulation of Amyloid Formation in Aging and Disease
As the population is aging, the incidence of age-related neurodegenerative diseases, such as Alzheimer and Parkinson disease, is growing. The pathology of neurodegenerative diseases is characterized by the presence of protein aggregates of disease specific proteins in the brain of patients. Under ce...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306383/ https://www.ncbi.nlm.nih.gov/pubmed/28261044 http://dx.doi.org/10.3389/fnins.2017.00064 |
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author | Stroo, Esther Koopman, Mandy Nollen, Ellen A. A. Mata-Cabana, Alejandro |
author_facet | Stroo, Esther Koopman, Mandy Nollen, Ellen A. A. Mata-Cabana, Alejandro |
author_sort | Stroo, Esther |
collection | PubMed |
description | As the population is aging, the incidence of age-related neurodegenerative diseases, such as Alzheimer and Parkinson disease, is growing. The pathology of neurodegenerative diseases is characterized by the presence of protein aggregates of disease specific proteins in the brain of patients. Under certain conditions these disease proteins can undergo structural rearrangements resulting in misfolded proteins that can lead to the formation of aggregates with a fibrillar amyloid-like structure. Cells have different mechanisms to deal with this protein aggregation, where the molecular chaperone machinery constitutes the first line of defense against misfolded proteins. Proteins that cannot be refolded are subjected to degradation and compartmentalization processes. Amyloid formation has traditionally been described as responsible for the proteotoxicity associated with different neurodegenerative disorders. Several mechanisms have been suggested to explain such toxicity, including the sequestration of key proteins and the overload of the protein quality control system. Here, we review different aspects of the involvement of amyloid-forming proteins in disease, mechanisms of toxicity, structural features, and biological functions of amyloids, as well as the cellular mechanisms that modulate and regulate protein aggregation, including the presence of enhancers and suppressors of aggregation, and how aging impacts the functioning of these mechanisms, with special attention to the molecular chaperones. |
format | Online Article Text |
id | pubmed-5306383 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53063832017-03-03 Cellular Regulation of Amyloid Formation in Aging and Disease Stroo, Esther Koopman, Mandy Nollen, Ellen A. A. Mata-Cabana, Alejandro Front Neurosci Neuroscience As the population is aging, the incidence of age-related neurodegenerative diseases, such as Alzheimer and Parkinson disease, is growing. The pathology of neurodegenerative diseases is characterized by the presence of protein aggregates of disease specific proteins in the brain of patients. Under certain conditions these disease proteins can undergo structural rearrangements resulting in misfolded proteins that can lead to the formation of aggregates with a fibrillar amyloid-like structure. Cells have different mechanisms to deal with this protein aggregation, where the molecular chaperone machinery constitutes the first line of defense against misfolded proteins. Proteins that cannot be refolded are subjected to degradation and compartmentalization processes. Amyloid formation has traditionally been described as responsible for the proteotoxicity associated with different neurodegenerative disorders. Several mechanisms have been suggested to explain such toxicity, including the sequestration of key proteins and the overload of the protein quality control system. Here, we review different aspects of the involvement of amyloid-forming proteins in disease, mechanisms of toxicity, structural features, and biological functions of amyloids, as well as the cellular mechanisms that modulate and regulate protein aggregation, including the presence of enhancers and suppressors of aggregation, and how aging impacts the functioning of these mechanisms, with special attention to the molecular chaperones. Frontiers Media S.A. 2017-02-14 /pmc/articles/PMC5306383/ /pubmed/28261044 http://dx.doi.org/10.3389/fnins.2017.00064 Text en Copyright © 2017 Stroo, Koopman, Nollen and Mata-Cabana. 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) or licensor 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 Stroo, Esther Koopman, Mandy Nollen, Ellen A. A. Mata-Cabana, Alejandro Cellular Regulation of Amyloid Formation in Aging and Disease |
title | Cellular Regulation of Amyloid Formation in Aging and Disease |
title_full | Cellular Regulation of Amyloid Formation in Aging and Disease |
title_fullStr | Cellular Regulation of Amyloid Formation in Aging and Disease |
title_full_unstemmed | Cellular Regulation of Amyloid Formation in Aging and Disease |
title_short | Cellular Regulation of Amyloid Formation in Aging and Disease |
title_sort | cellular regulation of amyloid formation in aging and disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306383/ https://www.ncbi.nlm.nih.gov/pubmed/28261044 http://dx.doi.org/10.3389/fnins.2017.00064 |
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