Abstract
The major components of the cholinergic receptor system of the human brain include projections from the basal forebrain nuclei, and utilize the two types of receptors that they synapse on, nicotinic and muscarinic acetylcholine receptors. With the widespread cortical and subcortical projections of the basal forebrain, activity of these two receptor systems provide modulation of neurotransmitter activity underlying normal cognitive processes, such as attention, episodic memory, and working memory. Alzheimer’s disease (AD) targets and damages cholinergic neurons in the basal forebrain, and as these projections are lost, cognitive performance progressively declines. Currently, the most widely prescribed treatment for AD is acetylcholinesterase inhibitor medications, which work by partially blocking the degradation of acetylcholine in the synapse and enabling more of the neurotransmitter to reach and activate cholinergic receptors. However since these medications have limited effectiveness, alternate treatments that focus on augmenting the activity of the receptors themselves, independent of acetylcholinesterase inhibition, are being explored. This review will discuss: 1) the role of the cholinergic system in modulating cognition, 2) novel cholinergic treatment strategies for AD-related cognitive decline, in particular treatments intended to increase cholinergic system activity by selectively targeting muscarinic and nicotinic acetylcholinergic receptors to improve cognitive performance, 3) risks, and additional considerations for cholinergic cognitive treatments for AD.
Keywords: Alzheimer’s disease, nicotinic, muscarinic, acetylcholine, α7 nicotinic receptor, α4Β2 nicotinic receptor, m1 muscarinic receptor, cholinergic agents.
Current Alzheimer Research
Title:Beyond Acetylcholinesterase Inhibitors: Novel Cholinergic Treatments for Alzheimer’s Disease
Volume: 14 Issue: 4
Author(s): Asante R. Kamkwalala and Paul A. Newhouse
Affiliation:
Keywords: Alzheimer’s disease, nicotinic, muscarinic, acetylcholine, α7 nicotinic receptor, α4Β2 nicotinic receptor, m1 muscarinic receptor, cholinergic agents.
Abstract: The major components of the cholinergic receptor system of the human brain include projections from the basal forebrain nuclei, and utilize the two types of receptors that they synapse on, nicotinic and muscarinic acetylcholine receptors. With the widespread cortical and subcortical projections of the basal forebrain, activity of these two receptor systems provide modulation of neurotransmitter activity underlying normal cognitive processes, such as attention, episodic memory, and working memory. Alzheimer’s disease (AD) targets and damages cholinergic neurons in the basal forebrain, and as these projections are lost, cognitive performance progressively declines. Currently, the most widely prescribed treatment for AD is acetylcholinesterase inhibitor medications, which work by partially blocking the degradation of acetylcholine in the synapse and enabling more of the neurotransmitter to reach and activate cholinergic receptors. However since these medications have limited effectiveness, alternate treatments that focus on augmenting the activity of the receptors themselves, independent of acetylcholinesterase inhibition, are being explored. This review will discuss: 1) the role of the cholinergic system in modulating cognition, 2) novel cholinergic treatment strategies for AD-related cognitive decline, in particular treatments intended to increase cholinergic system activity by selectively targeting muscarinic and nicotinic acetylcholinergic receptors to improve cognitive performance, 3) risks, and additional considerations for cholinergic cognitive treatments for AD.
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Cite this article as:
Kamkwalala R. Asante and Newhouse A. Paul, Beyond Acetylcholinesterase Inhibitors: Novel Cholinergic Treatments for Alzheimer’s Disease, Current Alzheimer Research 2017; 14 (4) . https://dx.doi.org/10.2174/1567205013666160930112625
DOI https://dx.doi.org/10.2174/1567205013666160930112625 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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