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Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein

The mechanisms underlying the selective targeting of specific brain regions by different neurodegenerative diseases is one of the most intriguing mysteries in medicine. For example, it is known that Alzheimer’s disease primarily affects parts of the brain that play a role in memory, whereas Parkinso...

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Autor principal: Jackson, Walker S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Limited 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882045/
https://www.ncbi.nlm.nih.gov/pubmed/24396151
http://dx.doi.org/10.1242/dmm.012146
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author Jackson, Walker S.
author_facet Jackson, Walker S.
author_sort Jackson, Walker S.
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description The mechanisms underlying the selective targeting of specific brain regions by different neurodegenerative diseases is one of the most intriguing mysteries in medicine. For example, it is known that Alzheimer’s disease primarily affects parts of the brain that play a role in memory, whereas Parkinson’s disease predominantly affects parts of the brain that are involved in body movement. However, the reasons that other brain regions remain unaffected in these diseases are unknown. A better understanding of the phenomenon of selective vulnerability is required for the development of targeted therapeutic approaches that specifically protect affected neurons, thereby altering the disease course and preventing its progression. Prion diseases are a fascinating group of neurodegenerative diseases because they exhibit a wide phenotypic spectrum caused by different sequence perturbations in a single protein. The possible ways that mutations affecting this protein can cause several distinct neurodegenerative diseases are explored in this Review to highlight the complexity underlying selective vulnerability. The premise of this article is that selective vulnerability is determined by the interaction of specific protein conformers and region-specific microenvironments harboring unique combinations of subcellular components such as metals, chaperones and protein translation machinery. Given the abundance of potential contributory factors in the neurodegenerative process, a better understanding of how these factors interact will provide invaluable insight into disease mechanisms to guide therapeutic discovery.
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spelling pubmed-38820452014-01-07 Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein Jackson, Walker S. Dis Model Mech Review The mechanisms underlying the selective targeting of specific brain regions by different neurodegenerative diseases is one of the most intriguing mysteries in medicine. For example, it is known that Alzheimer’s disease primarily affects parts of the brain that play a role in memory, whereas Parkinson’s disease predominantly affects parts of the brain that are involved in body movement. However, the reasons that other brain regions remain unaffected in these diseases are unknown. A better understanding of the phenomenon of selective vulnerability is required for the development of targeted therapeutic approaches that specifically protect affected neurons, thereby altering the disease course and preventing its progression. Prion diseases are a fascinating group of neurodegenerative diseases because they exhibit a wide phenotypic spectrum caused by different sequence perturbations in a single protein. The possible ways that mutations affecting this protein can cause several distinct neurodegenerative diseases are explored in this Review to highlight the complexity underlying selective vulnerability. The premise of this article is that selective vulnerability is determined by the interaction of specific protein conformers and region-specific microenvironments harboring unique combinations of subcellular components such as metals, chaperones and protein translation machinery. Given the abundance of potential contributory factors in the neurodegenerative process, a better understanding of how these factors interact will provide invaluable insight into disease mechanisms to guide therapeutic discovery. The Company of Biologists Limited 2014-01 /pmc/articles/PMC3882045/ /pubmed/24396151 http://dx.doi.org/10.1242/dmm.012146 Text en © 2014. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Review
Jackson, Walker S.
Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein
title Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein
title_full Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein
title_fullStr Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein
title_full_unstemmed Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein
title_short Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein
title_sort selective vulnerability to neurodegenerative disease: the curious case of prion protein
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882045/
https://www.ncbi.nlm.nih.gov/pubmed/24396151
http://dx.doi.org/10.1242/dmm.012146
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