ORGANOPHOSPHATES AND DELAYED NEUROPATHY - IS NTE ALIVE AND WELL
ORGANOPHOSPHATES AND DELAYED NEUROPATHY - IS NTE ALIVE AND WELL
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DOI：
10.1016/0041-008x(90)90036-t
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发表时间：
1990-03-01
影响因子：
3.8
通讯作者：
JOHNSON, MK
中科院分区：
文献类型：
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作者：
JOHNSON, MK
神经病靶标酯酶（NTE）是一种具有高酯酶催化活性的膜结合蛋白。该蛋白的生理功能尚不清楚，催化活性对神经轴突的健康不是必需的。然而，有压倒性的证据表明，通过共价结合某些有机磷酯修饰NTE的结构会引发不可逆的多发性神经病：这种事件可以监测。这一结论的实验证据进行审查，并解决了一些概念上的异议。NTE的研究已经成功预测了以下方面：（1）预防;（2）结构-活性关系，包括立体特异性;（3）长期低水平给予神经毒物的影响;以及（4）从（a）低剂量后观察到的NTE反应到高剂量后观察到的酶和临床效应，（B）从体外到体内，以及（c）从母鸡到人类反应的外推。考虑了NTE治疗开始与神经病变发生的后续事件之间的关系。NTE的纯化达到了可以获得用于神经生物学研究的抗体的程度。没有单一的严格的协议可以设计纳入NTE检测毒理学评价。建议的两阶段程序需要对第1阶段的解释来影响第2阶段的设计。
Neuropathy target esterase (NTE) is a membrane-bound protein with high esterase catalytic activity. The physiological function of the protein is not known and the catalytic activity is not essential to health of nerve axons. Nevertheless there is overwhelming evidence that modification of the structure of NTE by covalent binding of some organophosphorus esters initiates an irreversible polyneuropathy: this event can be monitored. The experimental evidence for this conclusion is reviewed and some conceptual objections are resolved. Studies of NTE have generated successful predictions concerning (1) prophylaxis; (2) structure-activity relationships including stereospecificity; (3) the effects of prolonged low-level administration of neurotoxicants; and (4) extrapolations from (a) NTE responses seen after low doses to enzyme and clinical effects seen after high doses, (b) from in vitro to in vivo, and (c) from hen to human responses. The relationship of initiation on NTE to subsequent events in development of neuropathy is considered. Purification of NTE is reaching the point where antibodies may be obtained for neurobiological study. No single rigid protocol can be devised for incorporation of NTE assays into toxicological evaluations. A proposed twostage procedure requires interpretation of Stage 1 to influence the design of Stage 2.