Referencia

Cysteine string protein-α prevents activity-dependent degeneration in GABAergic synapses, The Journal of Neuroscience 30:7377-91 (2010)

Autores

Pablo García-Junco-Clemente , Gloria Cantero ,Leonardo Gómez-Sánchez , Pedro Linares-Clemente, Jose A. Martínez-López , Rafael Luján, Rafael Fernández-Chacón.

Resumen

Nuestro trabajo ha puesto de manifiesto que los terminales nerviosos que mantienen una alta actividad neural necesitan de un co-chaperon molecular que les protege de la neurodegeneración sináptica. El co-chaperón es una proteina de las vesículas sinápticas denominada Cysteine String Protein-alfa (CSP-α). En ratones knock-out sin CSP-alfa las sinapsis de las neuronas más activas del hipocampo-las sinapsis de las neuronas en cesta que liberan GABA- tienen mayor tendencia a degenerar que otras sinapsis de neuronas vecinas menos activas. Curiosamente, en cultivos neuronales tratados farmacológicamente para disminuir la actividad neural, las mismas sinapsis sin CSP-α resisten significativamente a la degeneración.

Descripción

Imagen artículo Junio

REFERENCIA DEL GRUPO Y/O INVESTIGADOR
Las sinapsis son los puntos de contacto donde se produce la comunicación neuronal que subyace al correcto funcionamiento del cerebro. Los terminales nerviosos albergan vesículas sinápticas cargadas de neurotransmisores que se liberan tras la llegada de un impulso nervioso. Este fenómeno puede ocurrir miles de veces diariamente en terminales que se encuentran muy alejados del soma neuronal, como es el caso de las motoneuronas. Probablemente, los terminales nerviosos disponen de una maquinaria molecular que les permite mantener la función sináptica con autonomía del soma neuronal. El laboratorio de Rafael Fernández-Chacón está interesado en identificar los componentes de esta maquinaria y en entender su funcionamiento. Un elemento clave es una proteína de las vesículas sinápticas denominada Cysteine String Protein-alpha (CSP-alpha) Esta proteína está emparentada con los chaperones moleculares que participan en la recuperación y plegamiento de proteínas. Curiosamente, ratones modificados genéticamente que carecen de esta proteína presentan un fenotipo neurológico producido por una degeneración temprana de sus terminales nerviosos. En el trabajo publicado en Journal of Neuroscience hemos utilizado neuronas cultivadas de estos ratones que forman sinapsis "in vitro" y mediante técnicas electrofisiológicas hemos estudiado los detalles de la comunicación neuronal. Otra linea de trabajo estudia la dinámica del ciclo vesicular en la union neuromuscular utilizando técnicas de electrofisiología e imagen en ratones transgénicos que expresan marcadores fluorescentes del ciclo vesicular. Rafael Fernández-Chacón es Investigador del Instituto de Biomedicina de Sevilla (IBIS) Hosp.Univ.Virgen Rocio/CSIC/ Univ. de Sevilla, Profesor del Dpto. de Fisiología Médica y Biofísica en la Facultad de Medicina e Investigador de CIBERNED.

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