The many faces of EMMPRIN—Roles in neuroinflammation

The central nervous system (CNS) is a relatively immune-privileged organ, wherein a well-instated barrier system (the blood–brain barrier) prevents the entry of blood cells into the brain with the exception of regular immune surveillance cells. Despite this tight security immune cells are successful in entering the CNS tissue where they result in states of neuroinflammation, tissue damage and cell death. Various components of the blood–brain barrier and infiltrating cells have been examined to better understand how blood cells are able to breach this secure barrier. Proteases, specifically matrix metalloproteinases (MMP), have been found to be the common culprits in most diseases involving neuroinflammation. MMPs secreted by infiltrating cells act specifically upon targets on various components of the blood–brain barrier, compromising this barrier and allowing cell infiltration into the CNS. Extracellular matrix metalloproteinase inducer (EMMPRIN) is an upstream inducer of several MMPs and is suggested to be the master regulator of MMP production in disease states such as cancer metastasis. EMMPRIN in the context of the CNS is still relatively understudied. In this review we will introduce EMMPRIN, discuss its ligands and roles in non-CNS conditions that can help implicate its involvement in CNS disorders, showcase its expression within the CNS in healthy and disease conditions, elucidate its ligands and receptors, and briefly discuss the emerging roles it plays in various diseases of the CNS involving inflammation.