Glycocalyx Dysregulation Impairs the Blood–Brain Barrier in Aging and Disease

Key Words: Glycocalyx, blood-brain barrier, Mucin-type O-glycosylationThe blood-brain barrier (BBB) protects the central nervous system from harmful factors in circulating blood and plays a critical role in maintaining brain homeostasis and function.Its barrier function is maintained by tight junctions formed by brain endothelial cells, and it has extremely low transcytotic activity and high transporter selectivity [Chow & Gu (2015) Trends Neurosci.38, 598-608; Banks et al. (2021) Nat.Aging 1, 243-254].In addition, diverse glycoproteins, glycolipids, and proteoglycans are found on the surfaces of many cell types.The network structure primarily composed of these glycans is called the glycocalyx.This glycocalyx is particularly well-developed and is thought to be functional in animal cells.Vascular endothelial cells (VECs) are no exception and possess a glycocalyx that has been investigated in several studies.However, the glycan composition and function of the VEC glycocalyx in the blood-brain barrier remain unknown.Notably, a key pathological feature of aging and neurodegenerative diseases is the impairment of BBB barrier function [Sweeney et al. (