Alzheimer's Disease: Targeting the Cholinergic System
By Talita H. Ferreira-Vieira, Isabella M. Guimarães, Flavia R. Silva, F. M. Ribeiro. Current Neuropharmacology, 2016
1,218 citations recorded by the source corpus.
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.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Pharmacology
View Paper: https://www.semanticscholar.org/paper/80f3e4f8cea8efb6fc7b8b80dfc2485e1583d31e
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Citations in the corpus
- Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders (2021, background): “Its dysregulation is closely associated with neurodegenerative diseases such as AD [55,56].”
- The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review (2016, background): “Though acetylcholine is involved in cognitive processes such as memory, and decreased central cholinergic levels have been found in Alzheimer’s disease [230], little has been done to investigate the involvement of acetylcholine in acute exerciseinduced improvements in cognitive function.”
- Comprehensive Review on Alzheimer’s Disease: Causes and Treatment (2020, background): “Developing drugs that are capable of increasing CHT1 at the plasma membrane may become the future therapy of AD [36].”
- Anti-saccade as a Tool to Evaluate Neurocognitive Impairment in Alcohol Use Disorder (2022, background): “A growing consensus that AUD and AD share common disease pathophysiology is the dysfunction in the cholinergic system in the brain, which probably can explain the preclinical abnormity showed in anti-saccade tasks (89, 90).”