INVESTIGADORES
BOUZAT Cecilia Beatriz
congresos y reuniones científicas
Título:
Allosteric modulation of alpha7 nicotinic receptors by flavonoids
Autor/es:
NIELSEN, B.E.; BERMUDEZ, I.; BOUZAT, C.
Lugar:
Córdoba
Reunión:
Congreso; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias ( SAN); 2018
Institución organizadora:
Sociedad Argentina de Investigación en Neurociencias (SAN)
Resumen:
Plants have emerged as a valuable source for neuroprotective compounds like flavonoids. These polyphenolic compounds decrease neurotoxicity and the development of neurodegeneration. Potentiation of alpha7 nicotinic receptor, which is involved in cognition and memory, is a potential therapeutic strategy in neurodegenerative disorders. In particular, positive allosteric modulators (PAMs) are emerging as the best therapeutic tools. Some flavonoids have been reported as ligands for alpha7, but the molecular mechanisms underlying this interaction remain unknown. Our main goal is to unravel the molecular basis of flavonoid action at alpha7 by electrophysiological techniques. We analysed the effects of prototypes of distinct classes of flavonoids: quercetin, genistein and 7-dihydroxy-4-phenylcoumarin (neoflavonoid) on alpha7 activity. At the macroscopic level, the three compounds increased the peak current elicited by acetylcholine with minimal effects on desensitization, indicating that they behave as type I PAMs. At the single-channel level, they increased, with different efficacies, the duration of the open state. By analyzing the effects of flavonoids on mutant and chimeric alpha7 receptors we found that they share the transmembrane structural determinants of potentiation known for other PAMs. We conclude that, in addition to the well-known effects as antioxidants, the unique properties of flavonoids as natural alpha7 PAMs make them candidate compounds for the treatment of neurodegenerative disorders.