Ependymal cells and neurodegenerative disease: outcomes of compromised ependymal barrier function

Abstract Within the central nervous system, ependymal cells form critical components of the blood-cerebrospinal fluid barrier and the cerebrospinal fluid-brain barrier. These barriers provide biochemical, immunological and physical protection against the entry of molecules and foreign substances into the cerebrospinal fluid while also regulating cerebrospinal fluid dynamics, such as the composition, flow and removal of waste from the cerebrospinal fluid. Previous research has demonstrated that several neurodegenerative diseases, such as Alzheimer’s disease and multiple sclerosis, display irregularities in ependymal cell function, morphology, gene expression and metabolism. Despite playing key roles in maintaining overall brain health, ependymal barriers are largely overlooked and understudied in the context of disease, thus limiting the development of novel diagnostic and treatment options. Therefore, this review explores the anatomical properties, functions and structures that define ependymal cells in the healthy brain, as well as the ways in which ependymal cell dysregulation manifests across several neurodegenerative diseases. Specifically, we will address potential mechanisms, causes and consequences of ependymal cell dysfunction and describe how compromising the integrity of ependymal barriers may initiate, contribute to, or drive widespread neurodegeneration in the brain.