Amyloid beta-peptide decreases alpha-7 receptor potentiation

URANGA, R.M.; BOUZAT, C. ; LASALA, M.; ANTOLLINI, S.S.; FABIANI, C.; CORRADI, J.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades Biomédicas; 2017

Amyloid β peptide (Aβ) is a key player in the development ofAlzheimer disease (AD). Aβ is visible as the primary componentof senile plaques in the brains of Alzheimer?s patients. Cholinergicactivity mediated by human α7 nicotinic receptors is decreased inAD, and potentiation of α7 by positive allosteric modulators (PAMs)is emerging as a novel therapeutic strategy for improving memoryand cognition. There are reports showing functional interaction of Aβwith α7, but the reported effects are very varied and the underlyingmechanisms are not clear. Here we explored the effect of Aβ1-40and Aβ1-42 on human α7 at the patch-clamp single-channel level.α7 channel activity elicited by 100 µM ACh consists of brief and iso-lated openings. In the presence of PAMs, open channel lifetime isincreased and openings appear grouped in long activation episodes.The type II PAM PNU-120596 (1 µM) prolongs open durations andelicits activation episodes of ~2 s. In the presence of Aβ there isa statistically significant decrease in the mean duration of the potentiatedactivation episodes, which is 2.6-fold at 100 nM Aβ1-40(p