Cholinesterase Inhibitors: From Molecular Mechanisms of Action to Current and Future Prospects. From Molecular Mechanisms of Action to Current and Future Prospects

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) regulate the termination of cholinergic neurotransmission, signal transduction, and anti-inflammatory effects and have other, nonclassical activities. Cholinesterase functioning is essential for vital functions and is impaired in many pathologies, including Alzheimer's and Parkinson's diseases, anxiety disorders, ischemic stroke, cardiovascular disease, and autoimmune syndromes. Correspondingly, cholinesterase inhibitors have been developed both as therapeutics and as neurotoxic agents, in chemical warfare and as agricultural insecticides. Exposure to anti-ChE results in cholinergic hyperexcitation and modified levels and composition of cholinesterases with multisystem acute effects that can be lethal or result in long-term consequences that underscore the broad anatomical distribution of the mammalian cholinergic system. In this chapter, we introduce the cholinesterases and discuss the current understanding of their involvement in short- and long-term effects of anti-ChE exposure; we also cover current efforts to detect anti-ChEs and mitigate their effects and discuss the future directions of research and development in this field.