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.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Circadian Control of Heparan Sulfate Levels Times Phagocytosis of Amyloid Beta Aggregates. G. T. Clark, Y. Yu, C. A. Urban, G. Fu, C. Wang, F. Zhang, R. J. Linhardt, J. M. Hurley, PLOS Genetics, 18(2): e1009994, 2022.
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.
PLOS Genetics, 18(2): e1009994
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