A repurposed drug screen for regulating metabolic disease: an overview in the management of traumatic brain injury
Resumen
Introducción y antecedentes. El objetivo de este estudio es revisar los enfoques mecanicistas y las oportunidades terapéuticas en el manejo de las lesiones cerebrales traumáticas.
Métodos. Se ha descubierto una gran cantidad de medicamentos reutilizados por casualidad en el laboratorio o mediante un seguimiento cuidadoso de la acción del fármaco en la clínica y el análisis retrospectivo de los hallazgos clínicos. Las estatinas se usan ampliamente para tratar la hiperlipidemia y prevenir enfermedades cardiovasculares, aunque su aplicación como agentes neuroprotectores que debilitan el daño neurológico secundario aún es limitada en la lesión cerebral traumática (TBI). Sus otros mecanismos de acción no mediados por el colesterol (es decir, pleiotrópicos) incluyen hasta regula la expresión de la sintasa de óxido nítrico endotelial, mejora la neurogénesis y la sinaptogénesis y los efectos antiapoptóticos, aumenta la angiogénesis y varios mecanismos antioxidantes y antiinflamatorios.
Resultados. Casi todos los estudios han respaldado el papel potencial de las estatinas en la neuroprotección, y algunos se han centrado principalmente en sus efectos en modelos de lesiones cerebrales traumáticas. Se crean canales de potasio sensibles al ATP (KATP), que se pueden demostrar en las células de los islotes pancreáticos y en ciertas neuronas. El receptor potencial transitorio de melastatina 4 (TRPM4) es la segunda subunidad formadora de poros de SUR1. Se ha observado la regulación positiva de SUR1 y la apertura de SUR1-TRPM4 en los diferentes modelos relacionados con lesiones del sistema nervioso central (SNC), como TBI. Las sulfonilureas pueden prevenir la degeneración neuronal y mejorar los resultados cognitivos posteriores a una TBI al inhibir el canal SUR1-TRPM4.
Conclusión. La reutilización de medicamentos, conocida como reposicionamiento de medicamentos, se considera un método para volver a desarrollar un compuesto para utilizarlo en una enfermedad específica, que ahora se está convirtiendo en un procedimiento cada vez más necesario para los investigadores industriales y la comunidad académica.
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