Estudio molecular de la maquinaria de transporte intracelular en neuronas de animales transgénicos para la enfermedad de Huntington

BORGONOVO J; CAPELLA P; CICHINELLI C; SARTOR T; ROTH G; LUCAS JJ; SOSA MA

Los Cocos (Córdoba)

Congreso; XXII Reunión Anual Sociedad Argentina de Investigación en Neurociencias; 2007

Sociedad Argentina de Investigación en Neurociencias

Polyglutamine expansion (poliQ) in the protein huntingtin is pathogenic and responsible for the neuronal toxicity associated with Huntington´s disease (HD). The neurophatology of HD involves a significant dysfunction and death of neurons, particularly the medium spiny neurons of the striatum. Huntingtin (htt) is a cytoplasmic protein that interacts with proteins involved in vesicle trafficking like HIP1. The aim of this work was to evaluated if the expression of poliQ huntingtin modifys the levels and distribution of protein involved in receptor-mediated endocytosis. The levels of AP-2, dynamin and HIP1 in cytosolic and membrane fraction from different brain areas of transgenic mice of HD (HD94)  were determinated by Westernblot. Also, we analyzed this proteins in striatal cell lines established from wild-type and HdhQ111 kock-in embryos (Q111). We found an important decrease membrane levels of AP-2 and an increment in the corresponding cytosolic fraction in the striatum when poliQhtt is expressed. We didn´t find changes in the other protein. These result suggest that mutant huntingtin affects the normal distribution of AP-2 and it may contributes the pathogenesis of HD modifaiting  the clathrin mediated endocytosis of the striatal neurons.