Regulación de la Excitabilidad Neuronal y Epileptogénesis. Parte I

Abstract

The intracellular pathways of potentially epileptogenic signals were described through the study of metabotropic glutamate receptors (mGluRs). A narrative review of the literature was conducted, based on evidence that G-protein-coupled receptors play critical roles in modulating neuronal excitability. The net effect is the potentiation of NMDAR currents. Three challenging findings are highlighted: 1) A reduction in the expression of GIPC1 (GAIP-interacting protein, C terminus) was observed in both patients with temporal lobe epilepsy (TLE) and in mice with kainic acid-induced epilepsy. Moreover, GIPC1 was found to colocalize with mGluR7, and its overexpression counteracted epileptogenesis through the upregulation of mGluR7; 2) Positive upregulation of postsynaptic Homer 1a may protect against neuronal damage by reducing levels of phosphorylated extracellular signal-regulated kinase (ERK), thereby controlling seizures and preventing epileptogenesis; and 3) In kindled rats, overexpression of neuropeptide Y (NPY) acted as a protective factor. NPY has been identified as being synthesized in GABAergic neurons and functions as a neurotransmitter expressed in interneurons during cellular communication. These findings point to three promising targets for the development of new antiepileptic drugs, whether as monotherapies or in synergistic combinations. In addition, downstream proteins of mGluRs, such as those involved in the ERK/MAPK, mTOR, PLC, PKC, and CaM pathways, may also represent valuable therapeutic targets.