Symposium introduction: retrospect and prospects for neuropathy target esterase (NTE) and the delayed polyneuropathy...

This article introduces a Symposium devoted to Neuropathy Target Esterase (NTE). The characteristics of the disorder known as OPIDP are described and the steps by which NTE was identified as the target are summarised. Studies with many organophosphates, phosphinates and chiral phosphonates are entirely consistent with a 2-step process of initiation referred to as 'NTE (70-80%) aging': about 70-80% of available nervous system NTE is first covalently phosphylated causing inhibition of esterase activity, and then the molecules of inhibited NTE undergo a covalent bond-cleavage leaving a negative charge in the region of the still-bound phosphorus. This understanding has clarified structure/activity studies of neuropathic potential of OP esters and is now routinely applied in toxicological evaluations for regulatory purposes. However, the biological function of NTE has remained a mystery. Prospective views of the role of NTE are presented by different authors. Attempts to isolate catalytically active or radiolabelled inhibited NTE are near to success. Since the Symposium, complete isolation of NTE affinity-purified from hen brain has been reported (see M.K. Johnson & P. Glynn, Toxicologist, 13 (1993) 211, Abstr. 773). Some minor, but possibly significant, differences in properties of a soluble and a membrane-bound form of NTE in sciatic nerve has been identified. The nature of the disturbance brought about by covalent binding of organophosphoramidates at the active site of NTE and the discovery that 'non-aging' inhibitors of NTE can promote neuropathy in hens given a sub-neuropathic dose of neuropathic OPs has led to a concept of NTE inhibitors having a range of 'partial agonist' effects at the covalent binding site. Evidence is emerging that the promotion target may be 'cousin-of NTE' with very similar inhibition characteristics and a function in the processes of response to or repair of axonal damage.