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Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates
Alzheimer’s Disease (AD) is a neuroinflammatory disease characterized partly by the inability to clear, and subsequent build-up, of amyloid-beta (Aβ). AD has a bi-directional relationship with circadian disruption (CD) with sleep disturbances starting years before disease onset. However, the molecul...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830681/ https://www.ncbi.nlm.nih.gov/pubmed/35143487 http://dx.doi.org/10.1371/journal.pgen.1009994 |
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author | Clark, Gretchen T. Yu, Yanlei Urban, Cooper A. Fu, Guo Wang, Chunyu Zhang, Fuming Linhardt, Robert J. Hurley, Jennifer M. |
author_facet | Clark, Gretchen T. Yu, Yanlei Urban, Cooper A. Fu, Guo Wang, Chunyu Zhang, Fuming Linhardt, Robert J. Hurley, Jennifer M. |
author_sort | Clark, Gretchen T. |
collection | PubMed |
description | Alzheimer’s Disease (AD) is a neuroinflammatory disease characterized partly by the inability to clear, and subsequent build-up, of amyloid-beta (Aβ). AD has a bi-directional relationship with circadian disruption (CD) with sleep disturbances starting years before disease onset. However, the molecular mechanism underlying the relationship of CD and AD has not been elucidated. Myeloid-based phagocytosis, a key component in the metabolism of Aβ, is circadianly-regulated, presenting a potential link between CD and AD. In this work, we revealed that the phagocytosis of Aβ42 undergoes a daily circadian oscillation. We found the circadian timing of global heparan sulfate proteoglycan (HSPG) biosynthesis was the molecular timer for the clock-controlled phagocytosis of Aβ and that both HSPG binding and aggregation may play a role in this oscillation. These data highlight that circadian regulation in immune cells may play a role in the intricate relationship between the circadian clock and AD. |
format | Online Article Text |
id | pubmed-8830681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88306812022-02-11 Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates Clark, Gretchen T. Yu, Yanlei Urban, Cooper A. Fu, Guo Wang, Chunyu Zhang, Fuming Linhardt, Robert J. Hurley, Jennifer M. PLoS Genet Research Article Alzheimer’s Disease (AD) is a neuroinflammatory disease characterized partly by the inability to clear, and subsequent build-up, of amyloid-beta (Aβ). AD has a bi-directional relationship with circadian disruption (CD) with sleep disturbances starting years before disease onset. However, the molecular mechanism underlying the relationship of CD and AD has not been elucidated. Myeloid-based phagocytosis, a key component in the metabolism of Aβ, is circadianly-regulated, presenting a potential link between CD and AD. In this work, we revealed that the phagocytosis of Aβ42 undergoes a daily circadian oscillation. We found the circadian timing of global heparan sulfate proteoglycan (HSPG) biosynthesis was the molecular timer for the clock-controlled phagocytosis of Aβ and that both HSPG binding and aggregation may play a role in this oscillation. These data highlight that circadian regulation in immune cells may play a role in the intricate relationship between the circadian clock and AD. Public Library of Science 2022-02-10 /pmc/articles/PMC8830681/ /pubmed/35143487 http://dx.doi.org/10.1371/journal.pgen.1009994 Text en © 2022 Clark et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Clark, Gretchen T. Yu, Yanlei Urban, Cooper A. Fu, Guo Wang, Chunyu Zhang, Fuming Linhardt, Robert J. Hurley, Jennifer M. Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates |
title | Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates |
title_full | Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates |
title_fullStr | Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates |
title_full_unstemmed | Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates |
title_short | Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates |
title_sort | circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830681/ https://www.ncbi.nlm.nih.gov/pubmed/35143487 http://dx.doi.org/10.1371/journal.pgen.1009994 |
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