Year: 2022
Type: article
Abstract: 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.
Source: PLoS Genetics
Institutions: Rensselaer Polytechnic Institute, Chinese Academy of Sciences
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,655
Funders: National Science Foundation, Warren Alpert Foundation, Rensselaer Polytechnic Institute, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: An Automated Platform for the CE-MS Analysis of Glycosaminoglycans, CAREER: A Systems Biology Approach to Determine How Information from the Cellular Environment is Transduced to the Circadian Clock., G3431556290, The role ofglycosaminoglycan N-sulfation in glomerular biology/pathobiology, G5560935077, The Alzheimer's Disease Clinical and Translational Research (ADCTR) Training Program, G6671297155, Heparan Sulfate 3-O-Sulfation in Transcellular Propagation of Tauopathy in Alzheimer's Disease, Multiscale Modeling of Circadian Rhythms, Predoctoral Training Program for Alzheimer’s Disease at the Interface of Data Science, Engineering and Biology, Investigating Circadian Post-Transcriptional Regulation.
OpenAlex ID: W4226049253