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The interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration
Various neurodegenerative diseases are characterized by the accumulation of amyloidogenic proteins such as tau, α-synuclein, and amyloid-β. Prior to the formation of these stable aggregates, intermediate species of the respective proteins—oligomers—appear. Recently acquired data have shown that olig...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568959/ https://www.ncbi.nlm.nih.gov/pubmed/26053162 http://dx.doi.org/10.1111/acel.12359 |
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author | Deger, Jennifer M Gerson, Julia E Kayed, Rakez |
author_facet | Deger, Jennifer M Gerson, Julia E Kayed, Rakez |
author_sort | Deger, Jennifer M |
collection | PubMed |
description | Various neurodegenerative diseases are characterized by the accumulation of amyloidogenic proteins such as tau, α-synuclein, and amyloid-β. Prior to the formation of these stable aggregates, intermediate species of the respective proteins—oligomers—appear. Recently acquired data have shown that oligomers may be the most toxic and pathologically significant to neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The covalent modification of these oligomers may be critically important for biological processes in disease. Ubiquitin and small ubiquitin-like modifiers are the commonly used tags for degradation. While the modification of large amyloid aggregates by ubiquitination is well established, very little is known about the role ubiquitin may play in oligomer processing and the importance of the more recently discovered sumoylation. Many proteins involved in neurodegeneration have been found to be sumoylated, notably tau protein in brains afflicted with Alzheimer’s. This evidence suggests that while the cell may not have difficulty recognizing dangerous proteins, in brains afflicted with neurodegenerative disease, the proteasome may be unable to properly digest the tagged proteins. This would allow toxic aggregates to develop, leading to even more proteasome impairment in a snowball effect that could explain the exponential progression in most neurodegenerative diseases. A better understanding of the covalent modifications of oligomers could have a huge impact on the development of therapeutics for neurodegenerative diseases. This review will focus on the proteolysis of tau and other amyloidogenic proteins induced by covalent modification, and recent findings suggesting a relationship between tau oligomers and sumoylation. |
format | Online Article Text |
id | pubmed-4568959 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45689592015-10-01 The interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration Deger, Jennifer M Gerson, Julia E Kayed, Rakez Aging Cell Reviews Various neurodegenerative diseases are characterized by the accumulation of amyloidogenic proteins such as tau, α-synuclein, and amyloid-β. Prior to the formation of these stable aggregates, intermediate species of the respective proteins—oligomers—appear. Recently acquired data have shown that oligomers may be the most toxic and pathologically significant to neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The covalent modification of these oligomers may be critically important for biological processes in disease. Ubiquitin and small ubiquitin-like modifiers are the commonly used tags for degradation. While the modification of large amyloid aggregates by ubiquitination is well established, very little is known about the role ubiquitin may play in oligomer processing and the importance of the more recently discovered sumoylation. Many proteins involved in neurodegeneration have been found to be sumoylated, notably tau protein in brains afflicted with Alzheimer’s. This evidence suggests that while the cell may not have difficulty recognizing dangerous proteins, in brains afflicted with neurodegenerative disease, the proteasome may be unable to properly digest the tagged proteins. This would allow toxic aggregates to develop, leading to even more proteasome impairment in a snowball effect that could explain the exponential progression in most neurodegenerative diseases. A better understanding of the covalent modifications of oligomers could have a huge impact on the development of therapeutics for neurodegenerative diseases. This review will focus on the proteolysis of tau and other amyloidogenic proteins induced by covalent modification, and recent findings suggesting a relationship between tau oligomers and sumoylation. John Wiley & Sons, Ltd 2015-10 2015-06-05 /pmc/articles/PMC4568959/ /pubmed/26053162 http://dx.doi.org/10.1111/acel.12359 Text en © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Reviews Deger, Jennifer M Gerson, Julia E Kayed, Rakez The interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration |
title | The interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration |
title_full | The interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration |
title_fullStr | The interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration |
title_full_unstemmed | The interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration |
title_short | The interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration |
title_sort | interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration |
topic | Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568959/ https://www.ncbi.nlm.nih.gov/pubmed/26053162 http://dx.doi.org/10.1111/acel.12359 |
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