CONTRATADOS
GIRARDI Elena Silvia
artículos
Título:
Role for MDR-1 gene and other ABC transporters in refractory epilepsy? Review
Autor/es:
A LAZAROWSKI AND E GIRARDI
Revista:
Currents Topics in Neurochemistry
Editorial:
Research Trends
Referencias:
Lugar: India; Año: 2005 vol. 4 p. 51 - 51
ISSN:
0972-477X
Resumen:
ABSTRACT Over-expression of the drug transporter P-glycoprotein, encoded by the multidrug resistance gene MDR1, confers cross-chemoresistance in cancer to a wide range of non-related drugs or xenobiotics extruded from cells. MDR1 gene could play a role in the pathophysiology of pharmacoresistance in epilepsy. In the context of convulsive syndromes, several mechanisms can be involved in the up-regulation of this gene in the blood-brain barrier, and also inducing that different type of brain parenchyma cells over-express P-glycoprotein, developing the multi-drug resistance or refractory epilepsy phenotype, by limiting antiepileptic drug access to the epileptic focus. More recent reports have shown that the multidrug resistance-associated proteins, is also over-expressed in the blood-brain barrier and brain parenchyma cells of patients with drug resistant epilepsy, and the overexpression of both transporters could explain why refractory epileptic patients are resistant to a wide spectrum of antiepileptic drug with both different chemical properties, and mechanisms of anticonvulsant action. The abundant expression of P-glycoprotein and multidrug resistance-associated proteins in tissues or excretory organs where normally drug alteration takes place suggests that P-glycoprotein/ multidrug resistance-associated proteins plays central roles facilitating drug elimination. At date, several epilepsy experimental models have showed the brain overexpression of these transporters are directly related with the lack of protective effects of antiepileptic drug antiepileptic drug, and the inhibition of their pumping activities, can reverse the refractory phenotype. These studies demonstrated that a wide range of antiepileptic drug are substrates of these transporters, given molecular bases to the understanding of the multidrug resistance mechanisms in epilepsy.
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