Lester R. Drewes, PhD
Professor
Department of Biomedical Sciences
University of Minnesota Medical School, Duluth Campus

Brain Endothelial Cell Nutrient Transporters in Drug Delivery

With the benefit of genomic technologies, the identification of integral membrane proteins that function as transporters is nearly complete. These solute carriers are located in every cell of every organism and function to deliver substrates to their metabolic machinery, remove waste products, actively reject foreign chemicals, and maintain homeostasis between cells and their environment. Disruptions by mutations or inhibitors confirm the critical role of transporters and are the basis for diseases or toxic responses leading to pathologies. The vascular interface between blood and brain is a solid wall of endothelial cells with no gaps or spaces for diffusion. Therefore, transporters located in the luminal and abluminal membranes are the conduit for entry of essential substrates and the homeostatic maintenance of the brain microenvironment. Among the most active and critical transporters are GLUT1, MCT1, LAT1, ATA2 and MFSD2A. Because the specificity of transporters varies, they can also serve as passageways for pharmaceuticals designed to treat neurological diseases such as epilepsy, tumors, traumatic brain injury and psychological and neurodegenerative diseases. The design and delivery of drugs that effectively treat the target, but allow normal brain function, is one of the greatest challenges of neuromedicine today.