Blood-brain barrier dysfunction as a potential therapeutic target for neurodegenerative disorders

Abstract

The blood-brain barrier (BBB) is composed of specific tight junction proteins and transporters expressed on the lining of endothelial cells of the vasculature in the brain. The structural and functional integrity of the BBB is one of the most critical factors for maintaining brain homeostasis and is mainly regulated by complex interactions between various cell types, such as endothelial cells, pericytes, and astrocytes, which are shaped by their differential responses to changes in microenvironments. Alterations in these cellular components have been implicated in neurodegenerative disorders. Although it has long been considered that BBB dysfunction is a mere ramification of pathological phenomena, emerging evidence supports its critical role in the pathogenesis of various disorders. In epilepsy, heightened BBB permeability has been found to be associated with increased occurrence of spontaneous seizures. Additionally, exaggerated inflammatory responses significantly correlate with increased BBB permeability during healthy aging. Furthermore, it has been previously reported that BBB disruption can be an early marker for predicting cognitive impairment in the progression of Alzheimer's disease. We herein review a potential role of the major cellular components of the BBB, with a focus on the contribution of BBB disruption, in neurodegenerative disease progression.

Keywords: Aging; Alzheimer’s disease; Epilepsy; Extracellular matrix; Inflammation; Neuroglial interaction; Neurovascular unit.