Abstract
Cholinesterases are fundamental players in the peripheral and central nervous systems. These serine hydrolases are presented by two-membered families, namely acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
Under physiological conditions, AChE terminates the action of acetylcholine at synapses. The peculiar capacity of AChE also indicated, among others, its involvement in the differentiation of embryonic stem cells, neuritogenesis, cell adhesion, synaptogenesis, activation of dopamine neurons, amyloid beta fibre assembly, haematopoiesis and thrombopoiesis, or regulation of glutamate-mediated hippocampal activity.
For AChE, its abrupt blockade has fatal consequences. This phenomenon is typical for a class of highly toxic compounds-nerve agents and pesticides, which can irreversibly inhibit enzymes.
The role of BChE is still extensively discussed; it plays an important role in cholinergic mediation, it contributes to neurogenesis, and has detoxifying effect towards different xenobiotic drugs. It is also assumed that BChE overtakes the function of AChE in the case of malfunction.
Based on the abovementioned, both AChE and BChE are considered as highly relevant targets in the field of medicinal chemistry. For neurodegenerative disorders like Alzheimer's disease, there is a strong consensus that AChE and BChE targeting by reversible inhibitors can, at least temporarily, alleviate the symptoms associated with the disorder, and enhance the cognitive performance of individuals.
Other cholinesterase ligands, namely cholinesterase reactivators, typically endowed with strong nucleophilic function, can revert the irreversible action of organophosphorus compounds (nerve agents and pesticides). However, there are many other areas of research involving AChE and BChE, for example, pesticides; inflammation; and other neuronal disorders like Lewy body dementia, Parkinson's disease, myasthenia gravis, and so on.