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Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer’s disease: the role, regulation and restoration of LRP1
Amyloid beta (Aβ) homeostasis in the brain is governed by its production and clearance mechanisms. An imbalance in this homeostasis results in pathological accumulations of cerebral Aβ, a characteristic of Alzheimer’s disease (AD). While Aβ may be cleared by several physiological mechanisms, a major...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502358/ https://www.ncbi.nlm.nih.gov/pubmed/26236233 http://dx.doi.org/10.3389/fnagi.2015.00136 |
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author | Ramanathan, Anita Nelson, Amy R. Sagare, Abhay P. Zlokovic, Berislav V. |
author_facet | Ramanathan, Anita Nelson, Amy R. Sagare, Abhay P. Zlokovic, Berislav V. |
author_sort | Ramanathan, Anita |
collection | PubMed |
description | Amyloid beta (Aβ) homeostasis in the brain is governed by its production and clearance mechanisms. An imbalance in this homeostasis results in pathological accumulations of cerebral Aβ, a characteristic of Alzheimer’s disease (AD). While Aβ may be cleared by several physiological mechanisms, a major route of Aβ clearance is the vascular-mediated removal of Aβ from the brain across the blood-brain barrier (BBB). Here, we discuss the role of the predominant Aβ clearance protein—low-density lipoprotein receptor-related protein 1 (LRP1)—in the efflux of Aβ from the brain. We also outline the multiple factors that influence the function of LRP1-mediated Aβ clearance, such as its expression, shedding, structural modification and transcriptional regulation by other genes. Finally, we summarize approaches aimed at restoring LRP1-mediated Aβ clearance from the brain. |
format | Online Article Text |
id | pubmed-4502358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-45023582015-07-31 Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer’s disease: the role, regulation and restoration of LRP1 Ramanathan, Anita Nelson, Amy R. Sagare, Abhay P. Zlokovic, Berislav V. Front Aging Neurosci Neuroscience Amyloid beta (Aβ) homeostasis in the brain is governed by its production and clearance mechanisms. An imbalance in this homeostasis results in pathological accumulations of cerebral Aβ, a characteristic of Alzheimer’s disease (AD). While Aβ may be cleared by several physiological mechanisms, a major route of Aβ clearance is the vascular-mediated removal of Aβ from the brain across the blood-brain barrier (BBB). Here, we discuss the role of the predominant Aβ clearance protein—low-density lipoprotein receptor-related protein 1 (LRP1)—in the efflux of Aβ from the brain. We also outline the multiple factors that influence the function of LRP1-mediated Aβ clearance, such as its expression, shedding, structural modification and transcriptional regulation by other genes. Finally, we summarize approaches aimed at restoring LRP1-mediated Aβ clearance from the brain. Frontiers Media S.A. 2015-07-15 /pmc/articles/PMC4502358/ /pubmed/26236233 http://dx.doi.org/10.3389/fnagi.2015.00136 Text en Copyright © 2015 Ramanathan, Nelson, Sagare and Zlokovic. 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 and 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 Ramanathan, Anita Nelson, Amy R. Sagare, Abhay P. Zlokovic, Berislav V. Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer’s disease: the role, regulation and restoration of LRP1 |
title | Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer’s disease: the role, regulation and restoration of LRP1 |
title_full | Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer’s disease: the role, regulation and restoration of LRP1 |
title_fullStr | Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer’s disease: the role, regulation and restoration of LRP1 |
title_full_unstemmed | Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer’s disease: the role, regulation and restoration of LRP1 |
title_short | Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer’s disease: the role, regulation and restoration of LRP1 |
title_sort | impaired vascular-mediated clearance of brain amyloid beta in alzheimer’s disease: the role, regulation and restoration of lrp1 |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502358/ https://www.ncbi.nlm.nih.gov/pubmed/26236233 http://dx.doi.org/10.3389/fnagi.2015.00136 |
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