Publications by authors named "Andrew Franjesevic"
Article Synopsis
- Organophosphorus (OP) compounds, including G and V nerve agents and common pesticides, pose serious health risks, causing thousands of deaths annually due to their toxicity and the resulting cholinergic crisis from acetylcholine accumulation in the nervous system.
- Despite extensive research, no new treatments for OP exposure have emerged since the mid-1900s, with challenges including the need for effective reactivation of inhibited enzymes and crossing the blood-brain barrier.
- Recent developments in Mannich bases show promise, as they not only reactivate inhibited acetylcholinesterase (AChE) but can also restore activity to aged forms of the enzyme, signaling potential advances in therapeutic strategies against OP poisoning.
Article Synopsis
- Organophosphorus (OP) nerve agents inhibit acetylcholinesterase (AChE) and can lead to an irreversible aging process, making traditional reactivators ineffective.
- Researchers synthesized a set of quinone methide precursors (QMPs) to potentially reverse this aging process, focusing on a lead compound called C8.
- C8 successfully restored a significant percentage of activity to aged AChE, with its effectiveness influenced by pH levels, indicating potential for treating OP nerve agent exposure.
Acetylcholinesterase (AChE) is an essential enzyme that can be targeted by organophosphorus (OP) compounds, including nerve agents. Following exposure to OPs, AChE becomes phosphylated (inhibited) and undergoes a subsequent aging process where the OP-AChE adduct is dealkylated. The aged AChE is unable to hydrolyze acetylcholine, resulting in accumulation of the neurotransmitter in the central nervous system (CNS) and elsewhere.
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