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

Research output: Contribution to journalJournal articlepeer-review

Standard

Nicotinic Acetylcholine Receptors in the Pathophysiology of Alzheimer's Disease : The Role of Protein-Protein Interactions in Current and Future Treatment. / Thomsen, Morten Skøtt; Andreasen T., Jesper; Arvaniti, Maria; Kohlmeier, Kristi Anne.

In: Current Pharmaceutical Design, Vol. 22, No. 14, 2016, p. 2015-34.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Thomsen, MS, Andreasen T., J, Arvaniti, M & Kohlmeier, KA 2016, 'Nicotinic Acetylcholine Receptors in the Pathophysiology of Alzheimer's Disease: The Role of Protein-Protein Interactions in Current and Future Treatment', Current Pharmaceutical Design, vol. 22, no. 14, pp. 2015-34. https://doi.org/10.2174/1381612822666160127112357

APA

Thomsen, M. S., Andreasen T., J., Arvaniti, M., & Kohlmeier, K. A. (2016). Nicotinic Acetylcholine Receptors in the Pathophysiology of Alzheimer's Disease: The Role of Protein-Protein Interactions in Current and Future Treatment. Current Pharmaceutical Design, 22(14), 2015-34. https://doi.org/10.2174/1381612822666160127112357

Vancouver

Thomsen MS, Andreasen T. J, Arvaniti M, Kohlmeier KA. Nicotinic Acetylcholine Receptors in the Pathophysiology of Alzheimer's Disease: The Role of Protein-Protein Interactions in Current and Future Treatment. Current Pharmaceutical Design. 2016;22(14):2015-34. https://doi.org/10.2174/1381612822666160127112357

Author

Thomsen, Morten Skøtt ; Andreasen T., Jesper ; Arvaniti, Maria ; Kohlmeier, Kristi Anne. / Nicotinic Acetylcholine Receptors in the Pathophysiology of Alzheimer's Disease : The Role of Protein-Protein Interactions in Current and Future Treatment. In: Current Pharmaceutical Design. 2016 ; Vol. 22, No. 14. pp. 2015-34.

Bibtex

@article{482801ab5c294cf999e5386853d16a81,
title = "Nicotinic Acetylcholine Receptors in the Pathophysiology of Alzheimer's Disease: The Role of Protein-Protein Interactions in Current and Future Treatment",
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 related to differences in their ability to modulate nAChR protein interactions, rather than their effects on ion flow through the receptors. Drugs designed to target these interactions may thus provide a new avenue for drug development to ameliorate cognitive symptoms in AD. Notably, the development of experimental drugs that specifically modulate these interactions may provide the opportunity to selectively affect those aspects of nAChR function that are affected in AD.",
keywords = "Journal Article",
author = "Thomsen, {Morten Sk{\o}tt} and {Andreasen T.}, Jesper and Maria Arvaniti and Kohlmeier, {Kristi Anne}",
year = "2016",
doi = "10.2174/1381612822666160127112357",
language = "English",
volume = "22",
pages = "2015--34",
journal = "Current Pharmaceutical Design",
issn = "1381-6128",
publisher = "Bentham Science Publishers",
number = "14",

}

RIS

TY - JOUR

T1 - Nicotinic Acetylcholine Receptors in the Pathophysiology of Alzheimer's Disease

T2 - The Role of Protein-Protein Interactions in Current and Future Treatment

AU - Thomsen, Morten Skøtt

AU - Andreasen T., Jesper

AU - Arvaniti, Maria

AU - Kohlmeier, Kristi Anne

PY - 2016

Y1 - 2016

N2 - 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 related to differences in their ability to modulate nAChR protein interactions, rather than their effects on ion flow through the receptors. Drugs designed to target these interactions may thus provide a new avenue for drug development to ameliorate cognitive symptoms in AD. Notably, the development of experimental drugs that specifically modulate these interactions may provide the opportunity to selectively affect those aspects of nAChR function that are affected in AD.

AB - 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 related to differences in their ability to modulate nAChR protein interactions, rather than their effects on ion flow through the receptors. Drugs designed to target these interactions may thus provide a new avenue for drug development to ameliorate cognitive symptoms in AD. Notably, the development of experimental drugs that specifically modulate these interactions may provide the opportunity to selectively affect those aspects of nAChR function that are affected in AD.

KW - Journal Article

U2 - 10.2174/1381612822666160127112357

DO - 10.2174/1381612822666160127112357

M3 - Journal article

C2 - 26818866

VL - 22

SP - 2015

EP - 2034

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

SN - 1381-6128

IS - 14

ER -

ID: 166019508