Protocadherin gamma C3: a new player in regulating vascular barrier function

Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases, stroke, traumatic brain injury, and systemic diseases such as sepsis, viral and bacterial infections, and cancer. Compromised endothelial sealing leads to leaking blood vessels, followed by vasogenic edema. Brain edema as the most common complication caused by stroke and traumatic brain injury is the leading cause of death. Brain microvascular endothelial cells, together with astrocytes, pericytes, microglia, and neurons form a selective barrier, the so-called blood-brain barrier, which regulates the movement of molecules inside and outside of the brain. Mechanisms that regulate blood-brain barrier permeability in health and disease are complex and not fully understood. Several newly discovered molecules that are involved in the regulation of cellular processes in brain microvascular endothelial cells have been described in the literature in recent years. One of these molecules that are highly expressed in brain microvascular endothelial cells is protocadherin gamma C3. In this review, we discuss recent evidence that protocadherin gamma C3 is a newly identified key player involved in the regulation of vascular barrier function.