Perspectives Of P-Glycoprotein Modulation In Neurological Diseases: Pharmaceutical Approaches

The MDR1 gene product is P-glycoprotein (P-gp), a transmembrane protein that functions as an ATP-dependent pump. P-glycoprotein is a member of the ABC (ATP-binding cassette) superfamily, also known as ABCB1, MDR1 and PGY1.P-glycoprotein is expressed in different cell types and plays a determining role in absorption (intestine), distribution (CNS and leukocytes) and elimination (liver, kidney) of xenobiotics and endogenous products. The clinical significance of this protein is exemplified by the development of the drug resistance mechanism, which compromises the pharmaco-therapeutic approaches of various pathologies. One of the first mechanisms of drug resistance studied is associated with increased efflux of antibiotics in the bacterial cell. This pump is the most studied transporter and provides important details about the efflux pump mechanism.Modulating the expression of P-gp transporters is an effective therapeutic strategy for decreasing side effects and increasing drug efficacy, and for this reason there are used a number of methods for quantifying the expression of this protein. Molecular biochemistry offers extensive opportunities for MDR1 protein assay, some of them have been successfully implemented through collaboration between some research departments focused on related areas: the calcein inhibition assay, the expression of this protein on the neuroblastoma cells, and also in vivo amplification of P glycoprotein expression in the cerebral tissue, using monoclonal antibodies.