Alzheimer's disease: Targeting the Cholinergic System

H. Ferreira-Vieira, Talita; M. Guimaraes, Isabella; R. Silva, Flavia; M. Ribeiro, Fabiola

doi:10.2174/1570159x13666150716165726

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

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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Acetylcholinesterase (AChE) interacts with Aβ peptide and promotes plaque formation.
“AchE also interacts with Aβ peptide and promotes plaque formation [9].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [9]
Popular neuroprotective strategies for Alzheimer's disease management include discovering small molecules that block amyloid-beta interactions with intracellular and extracellular targets to avoid caspase activation and proapoptotic protein expression, reduce stress kinase signaling cascades, inhibit tau protein phosphorylation, counterbalance cholinergic functional loss, and boost neuronalplastic
“Popular neuroprotective strategies for AD management consist of discovering small molecules with the ability to block these Aβ interactions with intracellular and extracellular targets to avoid caspase activation and the expression of proapoptotic proteins, to reduce the stress kinase signaling cascades, to inhibit tau protein phosphorylation, to counterpoise cholinergic functional loss, and to bo”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [38]
Neuronal loss in AD has been related to dysregulation of the cholinergic system and glutamatergic system.
“Neuronal loss has also been related to the dysregulation of the cholinergic system and glutamatergic system (Ferreira-Vieira et al. 2016).”
From Alzheimer’s disease: Targeting the glutamatergic system (2020) · cites this paper as Ferreira-Vieira et al. 2016

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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: green
www.ncbi.nlm.nih.gov
Licence: cc-by-nc
Locations: Current Neuropharmacology (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Health Sciences › Medicine › Physiology › 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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Alzheimer's disease: Targeting the Cholinergic System

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