Abstract
This article describes acetylcholinesterase (AChE), an enzyme involved in parasympathetic neurotransmission, its activity, and how its inhibition can be pharmacologically useful for treating dementia, caused by Alzheimer’s disease, or as a warfare method due to the action of nerve agents. The chemical concepts related to the irreversible inhibition of AChE, its reactivation, and aging are discussed, along with a relationship to the current international legislation on chemical weapons.
Highlights
In 2018, events that occurred in SSaalliissbbuurryy aanndd AAmmeessbbuurryy, Great Britain, where a former Russian agent and other people were poisoned with an “unknown, high-purity grade military agent” with possible neurotoxic effffeccttss, proommpptteedd ddiissccuussssiioonnss aabboouutt the so-called “Novichokk” agents
We review the inhibition of cholinesterases and their outcome and how these chemical reactions can be subject of interest in tthhee ttrreeaattmmeenntt ooff nneeuurrooddeeggeenneerraattive ddiisseeases, lliikke AAllzzhheeimer’s disease (AD) or as method of warfare, which is forbiddenn bbyy tthhee CCWWCC
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Summary
In 2018, events that occurred in SSaalliissbbuurryy aanndd AAmmeessbbuurryy, Great Britain, where a former Russian agent and other people were poisoned with an “unknown, high-purity grade military agent” with possible neurotoxic effffeccttss,, proommpptteedd ddiissccuussssiioonnss aabboouutt the so-called “Novichokk” agents. ApSnpcdhliecBdautiflooenrs pa[1rr,ee3c,s4uu]rb.sdoSircvsh.ieddeudliens tawreo psuarbtds,ivAidaendd iBn, btweiongpAarftos,r Atoxainc dchBem, biceainlsganAd fBorfotropxirceccuhresmorisc.als and B for precuSSrccshhoeerddsu.ullee 11 lliisstt ttooxxiicc cchheemmiiccaallss wwhhiicchh hhaavvee bbeeeenn ddeevveellooppeedd oonnllyy ffoorr oorr uusseedd aass CCWW. OOnn ootthheerr hhaanndd,, tthheeiirr iirrrreevveerrssiibbllee iinnhhiibbiittiioonn ccaauusseedd bbyy nneerrvvee aaggeennttss ((FFiigguurreess 11––44)),, organophosphorus and carbamate pesticiddeess,, likee chlorrppyyrriiffooss 2222 and aldicaarrbb 23 (Figure 8) may be fatal, depending on the level ooff eexxppoossuurre aanndd iiffnnoottiiddeennttiiffiieeddaannddiimmmmeeddiiaatteellyyaaddddrreesssseedd[[6611––6677,,8844]]. AAss ddiissccuusssseedd,, AACChhEE iiss tthhee eennzzyymmee iinnvvoollvveedd iinn tthhee bbrreeaakkddoowwnn ooff AACChh 2255,, tthhee ppaarraassyymmppaatthheettiicc nneeuurroottrraannssmmiitttteerr,, iinnttoo cchhoolliinnee 2266 aanndd aacceettaattee 2277,, wwhhiicchh aarree rreeuuppttaakkeenn ffoorr ddee nnoovvoo ssyynntthheessiiss ooff tthhee nneeuurroottrraannssmmiitttteerr..TThheerreefoforree, ,AACChhEEisisaapphharamrmacaecuetuictiaclatlatragregte, ta,saistsitisnihnihbiitbiiotniopnrpovroovkoeskeasnainncirnecarseeaosef noef unroeutrraontsrmanisttmeritcteorncceonntrcaetniotrnataitontheatpothste-sypnoaspt-tsiycncalepftti,clecaldefint,glteoadexinagcertobateexdaccehroblainteedrgicchroelsinpeorngsiec orevseprotnhseenoevrvere tshtreunceturvreesstthruact truerqeusirtheaptarreaqsuyimreppaathraetsiycmstpimatuhleattiicosnt,imsuuclhataiosnn,esuurcohmaussncueularrojmunucstciuolnasr.
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