Efflux-Transporters at the Blood-Brain Barrier: Therapeutic Opportunities

ALAN TALEVI; LUIS E. BRUNO-BLANCH

Blood-brain barrier: new research

Nova Science publishers

Lugar: New York; Año: 2012;

ABC efflux transporters are ATP-dependent carriers responsible for regulating the entry of endogenous and exogenous compounds to certain body compartments and facilitating their elimination. Thus, they are especially expressed in barrier tissues (e.g. gut walls o blood-brain barrier) and in organs implicated in elimination functions (e.g. liver and kidneys). ABC transporters are characterized by wide-substrate specificity and they have been associated to multi-drug resistance issues. The level of expression of these transporters at the blood-brain barrier determines (at least partially) the inability of drugs from several therapeutic categories to reach their molecular targets in therapeutically effective concentrations. Here we will overview recent reports on expression, localization and regulation of ABC transporters at the blood-brain barrier, and their association to certain disorders: inflammation, epilepsy, brain cancer, Alzheimer’s disease. We will describe the therapeutic opportunities derived from these studies: development of ABC transporters inhibitors/modulators; modeling of novel drugs capable of avoiding recognition by efflux transporters, and; carrier systems designed to circumvent the biochemical component of the blood-brain barrier.