Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates.

Autor: Gretchen T Clark, Yanlei Yu, Cooper A Urban, Guo Fu, Chunyu Wang, Fuming Zhang, Robert J Linhardt, Jennifer M Hurley
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: PLoS Genetics, Vol 18, Iss 2, p e1009994 (2022)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1009994
Popis: 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.
Databáze: Directory of Open Access Journals
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