NTE: one target protein for different toxic syndromes with distinct mechanisms?

Bioessays. 2003 Aug;25(8):742-5. doi: 10.1002/bies.10322.

Abstract

Epidemics of organophosphate-induced delayed neuropathy (OPIDN) have paralysed thousands of people. This syndrome of nerve axon degeneration is initiated by organophosphates which react with neuropathy target esterase (NTE). Dosing experiments with adult chickens raise the possibility that OPIDN is initiated by a gain-of-function mechanism. By contrast, loss of NTE function by mutation causes massive apoptosis in Drosophila brain. Now, Winrow et al. show that nte(-/-) mice die by mid-gestation, but nte(+/-) mice appear hyperactive and are more sensitive than wild-type mice to a fatal form of OP toxicity. Thus, different toxic syndromes may be initiated via a single target protein.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Carboxylic Ester Hydrolases / antagonists & inhibitors
  • Carboxylic Ester Hydrolases / deficiency
  • Carboxylic Ester Hydrolases / genetics
  • Carboxylic Ester Hydrolases / metabolism*
  • Humans
  • Insecticides / toxicity
  • Mice
  • Mice, Knockout
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / enzymology
  • Organophosphorus Compounds
  • Syndrome

Substances

  • Insecticides
  • Organophosphorus Compounds
  • Carboxylic Ester Hydrolases
  • neurotoxic esterase
  • Acetylcholinesterase