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The Emerging Roles of Early Protein Folding Events in the Secretory Pathway in the Development of Neurodegenerative Maladies
Although, protein aggregation and deposition are unifying features of various neurodegenerative disorders, recent studies indicate that different mechanisms can lead to the development of the same malady. Among these, failure in early protein folding and maturation emerge as key mechanistic events t...
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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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293786/ https://www.ncbi.nlm.nih.gov/pubmed/28223916 http://dx.doi.org/10.3389/fnins.2017.00048 |
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author | Dubnikov, Tatyana Cohen, Ehud |
author_facet | Dubnikov, Tatyana Cohen, Ehud |
author_sort | Dubnikov, Tatyana |
collection | PubMed |
description | Although, protein aggregation and deposition are unifying features of various neurodegenerative disorders, recent studies indicate that different mechanisms can lead to the development of the same malady. Among these, failure in early protein folding and maturation emerge as key mechanistic events that lead to the manifestation of a myriad of illnesses including Alzheimer's disease and prion disorders. Here we delineate the cascade of maturation steps that nascent polypeptides undergo in the secretory pathway to become functional proteins, and the chaperones that supervise and assist this process, focusing on the subgroup of proline cis/trans isomerases. We also describe the chaperones whose failure was found to be an underlying event that initiates the run-up toward neurodegeneration as well as chaperones whose activity impairs protein homeostasis (proteostasis) and thus, promotes the manifestation of these maladies. Finally, we discuss the roles of aggregate deposition sites in the cellular attempt to maintain proteostasis and point at potential targets for therapeutic interventions. |
format | Online Article Text |
id | pubmed-5293786 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-52937862017-02-21 The Emerging Roles of Early Protein Folding Events in the Secretory Pathway in the Development of Neurodegenerative Maladies Dubnikov, Tatyana Cohen, Ehud Front Neurosci Neuroscience Although, protein aggregation and deposition are unifying features of various neurodegenerative disorders, recent studies indicate that different mechanisms can lead to the development of the same malady. Among these, failure in early protein folding and maturation emerge as key mechanistic events that lead to the manifestation of a myriad of illnesses including Alzheimer's disease and prion disorders. Here we delineate the cascade of maturation steps that nascent polypeptides undergo in the secretory pathway to become functional proteins, and the chaperones that supervise and assist this process, focusing on the subgroup of proline cis/trans isomerases. We also describe the chaperones whose failure was found to be an underlying event that initiates the run-up toward neurodegeneration as well as chaperones whose activity impairs protein homeostasis (proteostasis) and thus, promotes the manifestation of these maladies. Finally, we discuss the roles of aggregate deposition sites in the cellular attempt to maintain proteostasis and point at potential targets for therapeutic interventions. Frontiers Media S.A. 2017-02-07 /pmc/articles/PMC5293786/ /pubmed/28223916 http://dx.doi.org/10.3389/fnins.2017.00048 Text en Copyright © 2017 Dubnikov and Cohen. 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 Dubnikov, Tatyana Cohen, Ehud The Emerging Roles of Early Protein Folding Events in the Secretory Pathway in the Development of Neurodegenerative Maladies |
title | The Emerging Roles of Early Protein Folding Events in the Secretory Pathway in the Development of Neurodegenerative Maladies |
title_full | The Emerging Roles of Early Protein Folding Events in the Secretory Pathway in the Development of Neurodegenerative Maladies |
title_fullStr | The Emerging Roles of Early Protein Folding Events in the Secretory Pathway in the Development of Neurodegenerative Maladies |
title_full_unstemmed | The Emerging Roles of Early Protein Folding Events in the Secretory Pathway in the Development of Neurodegenerative Maladies |
title_short | The Emerging Roles of Early Protein Folding Events in the Secretory Pathway in the Development of Neurodegenerative Maladies |
title_sort | emerging roles of early protein folding events in the secretory pathway in the development of neurodegenerative maladies |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293786/ https://www.ncbi.nlm.nih.gov/pubmed/28223916 http://dx.doi.org/10.3389/fnins.2017.00048 |
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