Title:Alzheimer's disease: Targeting the Cholinergic System
Volume: 14
Issue: 1
Author(s): Talita H. Ferreira-Vieira, Isabella M. Guimaraes, Flavia R. Silva and Fabiola M. Ribeiro
Affiliation:
Keywords:
Acetylcholine, AChE, Alzheimer’s disease, ChAT, CHT1, VAChT.
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.
