[Recent advances in quantitative proteomics as a sensitive tool to quantify drug transporters and drug metabolizing enzymes at the human blood-brain barrier].

Since its discovery at the beginning of the 20th century, the blood-brain barrier (BBB) has been considered for a long time as a "physical barrier" able to limit brain distribution of highly molecular weight and/or polar compounds. This early concept of an anatomical barrier between the blood and the brain was supported by the finding of unique tight junctions between the brain endothelial cells so that they formed a continuous wall preventing the paracellular diffusion of solutes. In the middle of the 50's, BBB has been proposed as a "biochemical barrier" able to control the supply of brain to essential nutriments. More recently, BBB was evidenced as a key element in controlling effects of central nervous system drugs, since it plays a critical role in the uptake and efflux of drugs from the blood to the brain, or vice versa, hence affecting their concentrations and effects in the central nervous system (CNS). The BBB has therefore been more recently defined as a "pharmacological barrier" since the endothelial cells were found to contain a range of metabolizing enzymes and transporters that control the rate and extent of drugs reaching the brain parenchyma via transcellular pathway. The emergence of new quantitative proteomic approaches allows quantifying these transporters and enzymes at the BBB, opening the way to identify new drugs that may be targeted to the brain. © Société de Biologie, 2012.