Potentiation of human α4β2 neuronal nicotinic receptors by a Flustra foliacea metabolite

  title={Potentiation of human $\alpha$4$\beta$2 neuronal nicotinic receptors by a Flustra foliacea metabolite},
  author={Francisco Sala and Jos{\'e} Mulet and Krishna P. Reddy and Jos{\'e} Antonio Bernal and Philip Wikman and Luis M. Valor and Lars Peters and Gabriele Maria K{\"o}nig and Manuel Criado and Salvador Sala},
  journal={Neuroscience Letters},

Desformylflustrabromine Modulates α4β2 Neuronal Nicotinic Acetylcholine Receptor High- and Low-Sensitivity Isoforms at Allosteric Clefts Containing the β2 Subunit

Findings from this study will aid in the improved design of dFBr-like PAMs for potential therapeutic use and support the involvement of the principal face of the β2 subunit in dF Br modulation of ACh-induced responses.

Allosteric Modulator Desformylflustrabromine Relieves the Inhibition of α2β2 and α4β2 Nicotinic Acetylcholine Receptors by β-Amyloid1–42 Peptide

dFBr is a positive allosteric modulator for both α4β2 and α2β2 subtypes of nAChRs and that it also relieves the blockade of these receptors by Aβ1–42.

Targeting α4β2 nicotinic acetylcholine receptors in central nervous system disorders: perspectives on positive allosteric modulation as a therapeutic approach.

The present MiniReview is on the heteromeric α4β2 nAChR, as activity at this subtype contributes to cognitive functioning through interactions with multiple neurotransmitter systems and is implicated in various CNS disorders, for example schizophrenia and Alzheimer's disease.

Allosteric modulation and potential therapeutic applications of heteromeric nicotinic acetylcholine receptors

This review will discuss the primary lead compounds identified to date that allosterically potentiate or inhibit heteromeric nAChRs, including α4β2 and α3β4 subtypes, with a focus on the current understanding of these structural and functional relationships.

The Effects of β-Amyloid on α7 Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes

It is shown that human α7 subunit nAChRs are not activated by β-amyloid42 at 1 pM30 nM concentrations, and that short, seven-second applications of β-Amyloid interact with the α7 nA ChRs to alter the kinetics of the channel, however, the exact mechanism and pattern by which it effects the channel is still unclear.

Positive and negative modulation of nicotinic receptors.

  • H. Arias
  • Biology
    Advances in protein chemistry and structural biology
  • 2010



Neuronal nicotinic alpha 7 receptor expressed in Xenopus oocytes presents five putative binding sites for methyllycaconitine.

Analysis of MLA blockade and recovery of reconstituted heteromeric alpha 4 beta 2 receptors reveals, as expected, a time course compatible with only two binding sites for the toxin and, thus, further supports the validity of the model.

Chronic Exposure to Nicotine Upregulates the Human α4β2 Nicotinic Acetylcholine Receptor Function

Data indicate, in contrast to previous studies, that human α4β2 nAChRs are functionally upregulated by chronic nicotine exposure.

Unconventional ligands and modulators of nicotinic receptors.

The present article reviews and discusses the effects of unconventional ligands on nAChR activity and briefly describes the potential benefits of using some of these compounds in the treatment of neuropathologic conditions in which nA ChR function/expression is known to be altered.

Neuronal nicotinic receptors in the human brain

Alternate Stoichiometries of α4β2 Nicotinic Acetylcholine Receptors

Overnight treatment with nicotine increased the number of nAChRs and increased the proportion of the (alpha4)(2)(beta2)(3) stoichiometry, raising the possibility for an interesting mode of synaptic regulation for nicotinic signaling in the mammalian brain.

Nicotinic receptors in circuit excitability and epilepsy.

Since the thalamus and the cortex are strongly innervated by cholinergic neurons projecting from the brainstem and basal forebrain, an unbalance between excitation and inhibition, brought about by the presence of mutant receptors, could generate seizures by facilitating and synchronizing spontaneous oscillations in thalamo-cortical circuits.

Nicotinic receptors in aging and dementia.

Activation of neuronal nicotinic acetylcholine receptors (nAChRs) has been shown to maintain cognitive function following aging or the development of dementia. Nicotine and nicotinic agonists have