Experimental approaches for disrupting APP/Aâ interaction

BIGNANTE ELENA ANAHI; ZAá CESAR ALEXANDER; MORRONE RAFAEL

Huerta Grande, Córdoba Argentina

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2011

Sociedad Argentina de Investigación en Neurociencias (SAN)

Increasing evidence suggest that the interaction of Amyloid beta (Abeta) with its parental protein, the Amyloid beta Precursor protein  (APP), might play a pathogenic role in Alzheimer´s disease. It was suggested that the binding site sequence on APP is located in its extracellular juxtamembrane domain. Here, we describe two different experimental approaches for further defining the binding sequence.  First, we generated a series of point mutations within APP juxtamembrane domain.  These mutations were directed to specific aminoacids critical for beta sheet conformation.  Second, we used purified enantiomer or the racemic mix of different profens which have been described to bind to APP yuxtamembrane domain specifically. The effects of these approaches on Abeta-APP interaction was mainly analyzed by using cell cultures and coprecipitations assays.  The relevance of the results will be discussed.