Review article

https://doi.org/10.5599/admet.3.2.162

The complexity of roles of P-glycoprotein in refractory epilepsy: Pharmacoresistance, epileptogenesis, SUDEP and relapsing marker after surgical treatment

Alberto Lazarowski ; INFIBIOC, FFyB-University of Buenos Aires (UBA), Junin 956 (1113), CABA, Argentina
Liliana Czornyj ; Fundacion Investigar, Riobamba 426 P-15 (1025), CABA, Argentina
Luisa Rocha ; Pharmacobiology Department, Center for Research and Advanced Studies, DF, Mexico

Abstract

As described initially from clinical and experimental studies, P-glycoprotein (P-gp) plays a central role in the pharmacoresistance of epilepsy, acting by efflux of AEDs mainly at blood brain barrier (BBB) level. However, repetitive seizures can produce both brain and heart P-gp overexpression. Because P-gp activity induces membrane depolarization, its neuronal expression could be acting in the intrinsic mechanism of epileptogenesis, and its heart expression, can be a high risk factor of death, after severe-continuo convulsive stresses as in fatal status epilepticus or in SUDEP. Additionally, because P-gp is also a stem cell marker, we suggests that its constitutive overexpression in dysplastic neurons from brain epileptogenic areas observed in patients with refractory epilepsies, should be addressed as a risk factor of seizures relapse after surgical treatment. Here we discuss these concepts, based on our own clinical and experimental experiences, and reviewing the current literature on these subjects.

Keywords

P-glycoprotein; membrane depolarization; drug resistance; SUDEP, biomarker, long-term relapse

Hrčak ID:

140675

URI

https://hrcak.srce.hr/140675

Publication date:

1.7.2015.

Visits: 1.167 *