Pregledni rad

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

Sažetak

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.

Ključne riječi

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

Hrčak ID:

140675

URI

https://hrcak.srce.hr/140675

Datum izdavanja:

1.7.2015.

Posjeta: 1.487 *