Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) (AChE/BuChE)

Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) are the primary enzymes responsible for the hydrolysis of the neurotransmitter acetylcholine in the nervous system [1, 2]. AChE is predominantly found at neuromuscular junctions and in the brain's cholinergic synapses, where it rapidly terminates signal transmission [2, 3]. BuChE, often referred to as pseudocholinesterase, is found in plasma and glial cells and serves as a co-regulator of acetylcholine levels, particularly when AChE activity is compromised [3, 4]. In neurodegenerative conditions like Alzheimer's disease, the loss of cholinergic neurons leads to a deficit in acetylcholine, contributing to cognitive decline [5]. Therapeutic strategies often involve the use of cholinesterase inhibitors to block these enzymes, thereby increasing the availability of acetylcholine at the synaptic cleft to improve neurotransmission [1, 6]. While some drugs are selective for AChE, dual inhibitors targeting both AChE and BuChE are utilized to provide broader symptomatic relief, especially as BuChE activity tends to increase in the later stages of dementia [4, 6]. However, systemic inhibition can lead to adverse effects such as gastrointestinal distress and bradycardia due to overstimulation of the parasympathetic nervous system [1, 7].

Other names

CholinesterasePseudocholinesteraseTrue cholinesteraseAcetylcholine acetylhydrolaseButyrylcholine esteraseAcylcholine acylhydrolase

Reversible or pseudo-irreversible inhibition of the cholinesterase enzymes, preventing the breakdown of acetylcholine and increasing its availability at the synapse [1, 6].