Ubiquitously present in plants, flavonoids are a class of polyphe- nolic compounds comprising a benzopyrone moiety. These com- pounds have been reported to decline incidence rate and develop- ment of several neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Two flavonoids, genistein and quercetin, have been also described as type I positive allosteric modulators (PAMs) of α7 nicotinic acetylcholine receptor, which increase the amplitude of macroscopic responses evoked by ACh without chan- ging the desensitization rate. The molecular mechanism underlying these macroscopic effects remains unknown. Our main objective is to unravel the molecular basis of flavonoid allosteric potentiation of α7 at the single-channel level. Receptors were expressed in mam- malian cells and receptor function was evaluated by patch-clamp recordings. We analyzed the concentration-dependent effects of a prototype flavonoid for each class: quercetin as flavones, genistein as isoflavones and 5,7-dihydroxy-4-phenylcoumarin as neoflavo- noids. We here reported for the first time that neoflavonoids act as PAMs of α7. All flavonoids increased the mean open channel lifetime and the mean burst duration of α7, although the magnitude of the change differed among the different compounds. In order to define the structural and functional determinants of potentiation, we eva- luated flavonoid potentiation in an α7 receptor carrying a quintuple mutation at the transmembrane region that makes it insensitive to potentiation by type II PAMs and in a chimeric α7-5HT3 A receptor with the extracellular domain of α7 and the transmembrane region of 5-HT3 A. Statistically significance differences were established at p-values<0.05. We conclude that, in addition to the well-known effects as antioxidants, the unique properties of flavonoids as natu- ral α7 PAMs make them candidate drugs for the treatment of diffe- rent neurodegenerative disorders

LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; LXV Reunión Anual de la Sociedad Argentina de Inmunología; Reunión de la Sociedad Argentina de Andrología; XLVI Reunión Anual de la Sociedad Argentina de Biofísica; XIX Reunión Anual de la Sociedad Argentina de Biología; XLIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; Reunión Anual de la Sociedad Argentina de Fisiología; Reunión de la Sociedad Argentina de Hematología y XXIX Reunión Anual de la Sociedad Argentina de Protozoología

Fil: Nielsen, Beatriz Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina

Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Sociedad Argentina de Farmacología Experimental

Sociedad Argentina de Investigación Clínica

Sociedad Argentina de Protozoología

Sociedad Argentina de Inmunología

Sociedad Argentina de Hematología