RESUMEN
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.
Asunto(s)
Acetilcolinesterasa , Envejecimiento/metabolismo , Enfermedad de Alzheimer , Guerra Química/legislación & jurisprudencia , Inhibidores de la Colinesterasa/uso terapéutico , Agentes Nerviosos , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/enzimología , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas Ligadas a GPI/metabolismo , HumanosRESUMEN
Casualties caused by organophosphorus pesticides are a burden for health systems in developing and poor countries. Such compounds are potent acetylcholinesterase irreversible inhibitors, and share the toxic profile with nerve agents. Pyridinium oximes are the only clinically available antidotes against poisoning by these substances, but their poor penetration into the blood-brain barrier hampers the efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in future SAR studies, we evaluated neutral aryloximes as reactivators for paraoxon-inhibited Electrophorus eel acetylcholinesterase. Our findings may result into lead compounds, useful for development of more active compounds for emergencies and supportive care.