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LRRK2 como nueva diana terapéutica en retinosis pigmentaria

Authors: Usada Molinero, Eduardo de la; Zaldívar Diez de Bonilla, Josefa; Martínez González, Loreto; Martínez Gil, Ana;

LRRK2 como nueva diana terapéutica en retinosis pigmentaria

Abstract

La retinosis pigmentaria (RP) es un grupo heterogéneo de distrofias retinianas causado por mutaciones en múltiples genes. La RP cursa con disfunción y muerte progresiva de fotorreceptores, lo que causa una pérdida de visión cada vez mayor que termina con ceguera la mayoría de los casos. La enzima leucine- rich repeat kinase 2 (LRRK2) está implicada en procesos tanto inflamatorios como de muerte celular asociados a diferentes patologías neurodegenerativas, y por ello sus inhibidores son una buena estrategia terapéutica para el tratamiento de las mismas, sobre todo para la enfermedad de Parkinson. Dado que la retina neural puede considerarse la parte más externa del sistema nervioso central, en este trabajo se recogen los primeros datos que muestran la presencia de LRRK2 en un modelo de RP por qPCR, pudiendo ser considerada como una nueva diana terapéutica para el tratamiento de esta patología. Con el fin de buscar potenciales agentes terapéuticos para RP, hemos realizado estudios in vivo con un inhibidor de LRRK2. Este compuesto se administró sistemáticamente mediante inyección intraperitoneal a ratones rd10, modelo de RP, a partir del día postnatal 15 y durante diez días consecutivos para estudiar su potencial efecto neuroprotector, sobre la estructura e integridad de la retina, y su efecto antiinflamatorio analizando la localización de la microglía mediante inmunohistoquímica de criosecciones de retina de estos animales. La administración del compuesto parece atenuar la pérdida de fotorreceptores y la migración de la microglía, lo que podría preservar la capacidad visual y disminuir la inflamación que acompañan a la patología en ratones rd10. Nuestros resultados parecen mostrar un efecto neuroprotector de los fármacos inhibidores de LRRK2 en RP e indican el importante papel que puede tener este grupo de compuestos, y en especial SGP1.4, un derivado de isatina utilizado en este estudio, en un futuro tratamiento para esta patología

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Spain
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Keywords

Neurogénesis, Retina neural, Biología, Microglía, LRRK2, Pharmacy, Farmacia, Biology, Retinosis pigmentaria

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selected citations
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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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