Interplay between metalloproteinases and cell signalling in blood brain barrier integrity

The Blood-Brain Barrier (BBB) is a highly specialised interface separating the Central Nervous System (CNS) from circulating blood. Dysregulation of the BBB is a key early event in pathological conditions such as inflammation, in which the entry of activated leukocytes into the CNS is facilitated by BBB breakdown. The metzincin family of metalloproteinases (MPs) is one of the major contributors to BBB permeability as they cleave endothelial cell-cell contacts and underlying basal lamina components. However, the mechanisms by which MPs regulate BBB integrity has not yet been fully elucidated. The aim of this review is to provide an overview of pathways by which MPs could regulate the BBB in the context of neuroinflammation.