Title : Allosteric modulator Desformylflustrabromine relieves the inhibition of alpha2beta2 and alpha4beta2 nicotinic acetylcholine receptors by beta-amyloid(1-42) peptide - Pandya_2011_J.Mol.Neurosci_45_42 |
Author(s) : Pandya A , Yakel JL |
Ref : Journal of Molecular Neuroscience , 45 :42 , 2011 |
Abstract :
Nicotinic acetylcholine receptors (nAChRs) are pentameric transmembrane proteins that belong to the cys-loop ligand-gated ion channel family. These receptors are widely expressed in the brain and implicated in the pathophysiology of many neurological conditions, including Alzheimer's disease (AD), where typical symptoms include the loss of cognitive function and dementia. The presence of extracellular neuritic plaques composed of beta amyloid (Abeta(1-42)) peptide is a characteristic feature of AD. Desformylflustrabromine (dFBr) is a positive allosteric modulator (PAM) for alpha4beta2 nAChRs since it increases peak ACh responses without inducing a response on its own. Previously, the effect of dFBr on the alpha2beta2 nAChR subtype was not known. The action of dFBr was tested on alpha2beta2 receptors expressed in Xenopus oocytes. It was found that dFBr is also a PAM for the alpha2beta2 receptor. Next we tested whether dFBr had any effect on the previously known block of both the alpha4beta2 and alpha2beta2 receptors by Abeta(1-42). We found that the functional blockade of ACh-induced currents in oocytes expressing alpha4beta2 and alpha2beta2 receptors by Abeta(1-42) was prevented by dFBr. We conclude that dFBr is a positive allosteric modulator for both alpha4beta2 and alpha2beta2 subtypes of nAChRs and that it also relieves the blockade of these receptors by Abeta(1-42). This study demonstrates that PAMs for the non-alpha7 nAChRs have the potential to develop into clinically applicable drugs for AD and other disorders. |
PubMedSearch : Pandya_2011_J.Mol.Neurosci_45_42 |
PubMedID: 21424792 |
Pandya A, Yakel JL (2011)
Allosteric modulator Desformylflustrabromine relieves the inhibition of alpha2beta2 and alpha4beta2 nicotinic acetylcholine receptors by beta-amyloid(1-42) peptide
Journal of Molecular Neuroscience
45 :42
Pandya A, Yakel JL (2011)
Journal of Molecular Neuroscience
45 :42