Efforts toward treatments against aging of organophosphorus-inhibited acetylcholinesterase

• Published in: Annals of the New York Academy of Sciences 2016-06, Vol.1374 (1), p.94-104
• Main Authors: Zhuang, Qinggeng, Young, Amneh, Callam, Christopher S., McElroy, Craig A., Ekici, Özlem Dogan, Yoder, Ryan J., Hadad, Christopher M.
• Format: Article
• Language: English
• Subjects: acetylcholinesterase; Acetylcholinesterase - metabolism; Aging; Animals; Cholinesterase Inhibitors - toxicity; exogenous; Humans; Models, Biological; Organophosphorus Compounds - toxicity; realkylation; resurrection; Up-Regulation - drug effects; upregulation
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/nyas.13124

Aging is a dealkylation reaction of organophosphorus (OP)‐inhibited acetylcholinesterase (AChE). Despite many studies to date, aged AChE cannot be reactivated directly by traditional pyridinium oximes. This review summarizes strategies that are potentially valuable in the treatment against aging in OP poisoning. Among them, retardation of aging seeks to lower the rate of aging through the use of AChE effectors. These drugs should be administered before AChE is completely aged. For postaging treatment, realkylation of aged AChE by appropriate alkylators may pave the way for oxime treatment by neutralizing the oxyanion at the active site of aged AChE. The other two strategies, upregulation of AChE expression and introduction of exogenous AChE, cannot resurrect aged AChE but may compensate for lowered active AChE levels by in situ production or external introduction of active AChE. Upregulation of AChE expression can be triggered by some peptides. Sources of exogenous AChE can be whole blood or purified AChE, either from human or nonhuman species.