Beta-amyloid exhibits antagonistic effects on alpha 7 nicotinic acetylcholine receptors in orchestrated manner

• In low concentration and monomer forms Aβ not show any neurotoxicity but also they produce neuroprotective effects.
• The Aβ-induced neuroprotection is mediated via agonistic effects of monomers of Aβ on α7 nAChR.
• Oligomerization and accumulation of Aβ may block the neuroprotective function of α7 nAChR by the antagonistic effects.
• Peptide function may be related to three-dimensional, physical, and morphological characteristics of oligomers.
• Reducing of Aβ level and inhibition of peptide aggregation may be a useful strategies for the AD therapy.

Although beta-amyloid (Aβ) has been regarded as the principal toxic factor in the pathogenesis of Alzheimer’s disease (AD), it plays important physiological roles in phenomena such as neuron survival, synaptic plasticity, and memory formation. There are numerous plausible reasons to assume that all of the mentioned pathological and physiological functions of Aβ may be partially mediated via alpha 7 nicotinic acetylcholine receptor (nAChR). Agonistic and antagonistic aspects of Aβ on nAChRs may explain this paradox in peptide–receptor function. It seems that Aβ shows antagonistic effects on α7 nAChR in a dose-dependent manner, and its pathologic function may partially correlate with antagonization of the receptor.If this hypothesis is supported, the related mechanisms of neurotoxicity, neuroprotection, memory formation, and AD pathogenesis might be identified. In addition, such knowledge helps make a more valid interpretation of neuron signaling and a better design of AD animal models. In addition, it may provide new insights into AD therapy development via reducing the amount of Aβ and inhibiting peptide aggregation.

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