Nicotinic Acetylcholine Receptors in the Pathophysiology of Al zheimer's Disease: The Role of Protein-Protein Interactions in Current and Future Treatment

Current Pharmaceutical Design
Morten S ThomsenKristi Anne Kohlmeier

Abstract

Nicotinic acetylcholine receptors (nAChRs) have been pursued for decades as potential molecular targets to treat cognitive dysfunction in Alzheimer's disease (AD) due to their positioning within regions of the brain critical in learning and memory, such as the prefrontal cortex and hippocampus, and their demonstrated role in processes underlying cognition such as synaptic facilitation, and theta and gamma wave activity. Historically, activity at these receptors is facilitated in AD by use of drugs that increase the levels of their endogenous agonist acetylcholine, and more recently nAChR selective ligands have undergone clinical trials. Here we discuss recent findings suggesting that the expression and function of nAChRs in AD may be regulated by direct interactions with specific proteins, including Lynx proteins, NMDA-receptors and the Wnt/β-catenin pathway, as well as β-amyloid. The ability of protein interactions to modify nAChR function adds a new level of complexity to cholinergic signaling in the brain that may be specifically altered in AD. It is currently not known to what degree current nAChR ligands affect these interactions, and it is possible that the difference in the clinical effect of nAChR ligands in AD is relat...Continue Reading

Citations

Jun 28, 2016·Journal of Neurochemistry·Maria ArvanitiMorten S Thomsen
Jan 14, 2017·Medicinal Research Reviews·Sergey O BachurinAleksey A Ustyugov
May 1, 2021·International Journal of Molecular Sciences·Silvia MuccioliRoberto Costa

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