The reaction of alcohols and phosphoric acid yields organophosphate (OP) molecules that prevent the breakdown of the neurotransmitter acetylcholine (ACh) through inhibition of the hydrolytic activity of acetylcholinesterase (AChE). OPs were initially aimed to fight insects, but further developments turned them into chemical weapons (Gallo and Lawryk, 1991; Chambers et al., 2001). Within the central nervous system and in the neuromuscular junctions, AChE is vital for the transmission of cholinergic impulses. A closely similar enzyme, butyrylcholinesterase (BChE) is also capable of hydrolyzing ACh. It has been suggested that human BChE from plasma participates in the endogenous scavenging of naturally occurring drugs (e.g., physostigmine, cocaine), manmade therapeutics (e.g., succinylcholine), as well as anticholinesterase-based pesticides and chemical warfare agents (Raveh et al., 1993, 1997; Jbilo et al., 1994; Schwarz et al., 1995; Sun et al., 2002; Giacobini, 2004), and as such serves as an inherent protector from the short-term damages caused by neurotoxic agents (Glick et al., 2003). Consequently, BChE administration was proposed as a putative prophylactic and therapeutic treatment of OP-poisoned subjects (Doctor and Saxena, 2005). Preclinical studies in various experimental animal models (rats, mice, and monkeys) supported the notion that this treatment may be palliatively successful (Ashani et al., 1991; Doctor and Saxena, 2005). However, the dangers of OP poisoning are not limited to the immediate effects, and it remained unclear whether BChE administration per se would not entail long-term damages. This question became particularly important in view of findings that synaptic acetylcholinesterase (AChE-S) exacerbates the formation of amyloid fibrils, the primary neuropathology characteristic of Alzheimer’s disease (AD) (Inestrosa et al., 1996a, 1996b, 2005; Rees et al., 2003, 2005).
|Original language||American English|
|Title of host publication||Chemical Warfare Agents|
|Subtitle of host publication||Chemistry, Pharmacology, Toxicology, and Therapeutics|
|Number of pages||16|
|State||Published - 1 Jan 2007|
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