Expression de la P-glycoprotéine au niveau de la barrière hémato-encéphalique (BHE) : Implications pharmacologiques
(2014) Louvain médical — Vol. 133, n° 2, p. 87-97 (2014)
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- (en) The blood brain barrier (BBB) is not only a passive interface between the central nervous system (CNS) and the rest of the organism, but also exhibits dynamic characteristics due, in particular, to the involvement of P-glycoprotein (P-gp). Encoded by the MDR1/ABCB1 gene, this ATP-dependent efflux transporter is localized on the luminal side of BBB endothelial cells. By preventing the cerebral accumulation of numerous endogenous compounds and xenobiotics, P-gp plays a crucial role in CNS protection and detoxification. However, it was not P-gp’s physiological function that drew the attention of the scientific community, but rather its involvement in the multidrug resistance (MDR) phenotype pertaining to some cancers. To explain the reasons why P-gp is overexpressed in some cerebral tumors and so actively participates in anticancer treatment failures, researchers began to investigate the factors that modulate its expression and activity. At present, P-gp’s relevance has become well-accepted in the field of neurology. On one hand, the protein’s overexpression appears to be involved in resistance mechanisms against drugs used for cancer, epilepsy, and HIV treatments. On the other hand, its deficiency is suspected to be a risk factor for a higher incidence of central side-effects in relation to some treatments. This report was aimed to provide a review of the literature focused on this efflux transporter, while highlighting the P-gp’s role, modulation, and pharmacological implications. A better understanding of P-gp functioning could eventually open the door to new therapeutic targets.
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Achen, C., & Haufroid, V. (2014). Expression de la P-glycoprotéine au niveau de la barrière hémato-encéphalique (BHE) : Implications pharmacologiques. Louvain médical, 133(2), 87-97. https://hdl.handle.net/2078.5/50594 (Original work published 2014)