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Cited by 1,551Cholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatmentsNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 277 of the 277 references it cites were found in a registry or an index.

Alzheimer's disease: Targeting the Cholinergic System

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H. Ferreira-Vieira, Talita, M. Guimaraes, Isabella, R. Silva, Flavia, M. Ribeiro, Fabiola·2016·Current Neuropharmacology
DOI 10.2174/1570159x13666150716165726PMC PMC4787279
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Abstract

Acetylcholine (ACh) has a crucial role in the peripheral and central nervous systems. The enzyme choline acetyltransferase (ChAT) is responsible for synthesizing ACh from acetyl-CoA and choline in the cytoplasm and the vesicular acetylcholine transporter (VAChT) uptakes the neurotransmitter into synaptic vesicles. Following depolarization, ACh undergoes exocytosis reaching the synaptic cleft, where it can bind its receptors, including muscarinic and nicotinic receptors. ACh present at the synaptic cleft is promptly hydrolyzed by the enzyme acetylcholinesterase (AChE), forming acetate and choline, which is recycled into the presynaptic nerve terminal by the high-affinity choline transporter (CHT1). Cholinergic neurons located in the basal forebrain, including the neurons that form the nucleus basalis of Meynert, are severely lost in Alzheimer's disease (AD). AD is the most ordinary cause of dementia affecting 25 million people worldwide. The hallmarks of the disease are the accumulation of neurofibrillary tangles and amyloid plaques. However, there is no real correlation between levels of cortical plaques and AD-related cognitive impairment. Nevertheless, synaptic loss is the principal correlate of disease progression and loss of cholinergic neurons contributes to memory and attention deficits. Thus, drugs that act on the cholinergic system represent a promising option to treat AD patients.

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Crossref · 10.2174/1570159x13666150716165726

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Fig. (1) Schematic representation of biological aspects involving acetylcholine neurotransmission. Acetylcholine (ACh) is synthesized in the cytosol of cholinergic presynaptic neurons from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme choline acetyltransferase (ChAT) and is then transferred into synaptic vesicles by the vesicular acetylcholine transporter (VAChT). Depolarization of the presynaptic neuron promotes ACh exocytosis from synaptic vesicles into the synaptic cleft, where it can bind nicotinic or muscarinic receptors, leading to either a stimulatory or an inhibitory response. In the synaptic cleft, ACh is rapidly hydrolyzed by the enzyme acetylcholinesterase (AChE), releasing acetate and choline, which is reuptaken into the presynaptic cholinergic neuron by the high-affinity choline transporter (CHT1).
Fig. (1) Schematic representation of biological aspects involving acetylcholine neurotransmission. Acetylcholine (ACh) is synthesized in the cytosol of cholinergic presynaptic neurons from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme choline acetyltransferase (ChAT) and is then transferred into synaptic vesicles by the vesicular acetylcholine transporter (VAChT). Depolarization of the presynaptic neuron promotes ACh exocytosis from synaptic vesicles into the synaptic cleft, where it can bind nicotinic or muscarinic receptors, leading to either a stimulatory or an inhibitory response. In the synaptic cleft, ACh is rapidly hydrolyzed by the enzyme acetylcholinesterase (AChE), releasing acetate and choline, which is reuptaken into the presynaptic cholinergic neuron by the high-affinity choline transporter (CHT1).CC BY-NC · PubMed Central

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  1. [1]Loewi O. Über humerole übertragbarkeit der herznervenwirkung. I Mitteilung Pflugers Arch., 1921, 189, 239-242. 10. 1007/BF01738910 1921

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Metadata

Authors
H. Ferreira-Vieira, T., M. Guimaraes, I., R. Silva, F., & M. Ribeiro, F.
Venue
Current Neuropharmacology
Publisher
Bentham Science Publishers Ltd.
Published
2016-01-22
Volume
14
Issue
1
Pages
101-115
ISSN
1570-159X (ISSN-L)
DOI
10.2174/1570159x13666150716165726
PMC
PMC4787279
OpenAlex
W2261085470
Cited by
1,551
References
277
Citations by year
2026: 120 · 2025: 191 · 2024: 207 · 2023: 224 · 2022: 224 · 2021: 214 · 2020: 173 · 2019: 108 · 2018: 44 · 2017: 35 · 2016: 8
FWCI
52.31
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Current Neuropharmacology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Alzheimer's disease, cholinergic system, acetylcholine, choline acetyltransferase, vesicular acetylcholine transporter, acetylcholinesterase, choline transporter 1, muscarinic receptors, nicotinic acetylcholine receptors, cholinergic neurons, nucleus basalis of Meynert, synaptic loss, acetylcholinesterase inhibitors, cholinergic drugs
MeSH terms
Acetylcholine, Alzheimer Disease, Animals, Cholinesterase Inhibitors, Humans, Receptors, Cholinergic, Drug Delivery Systems, Cholinergic Agents, Cholinergic Neurons

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