RESUMEN
Certain forms of amyotrophic lateral sclerosis (ALS) are associated with an altered compartmentalization of FUS and its aggregation in the cytoplasm of motoneurons. FUS is a DNA/RNA-binding protein that is involved in DNA repair and the regulation of transcription, splicing, RNA transport, and local translation. Two theories have been proposed to explain the mechanism of the pathophysiological process in ALS. The theories attribute degeneration of motor neurons to either loss or gain of FUS function. The review describes the main physiological functions of FUS and considers evidence for each of the theories of ALS pathogenesis.
Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Neuronas Motoras/metabolismo , Agregación Patológica de Proteínas/genética , Proteína FUS de Unión a ARN/genética , Esclerosis Amiotrófica Lateral/patología , Reparación del ADN/genética , Humanos , Neuronas Motoras/patología , Empalme del ARN/genética , Proteína FUS de Unión a ARN/metabolismoRESUMEN
In this paper, we showed that in the cortex of mice expressing an abberant form of FUS protein that model amyotrophic lateral sclerosis (ALS), the processes of KCl-induced and basal [(3)H]glutamate release and uptake are altered at the presymptomatic stage as compared to the non-transgenic littermates. The change in these three parameters in transgenic animals causes excitotoxicity, which, in turn, may lead to massive loss of motor neurons and the onset of ALS symptoms.