ArticleProceedings of the National Academy of Sciences of the United States of America2003
Evidence that mouse brain neuropathy target esterase is a lysophospholipase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Neuropathy target esterase activity defines phenotypes among PNPLA6 disorders.Brain : a journal of neurology · 2024Pooled it
- Beyond Neurodegeneration: White Matter Vacuolation as a Primary Myelin Defect.International journal of molecular sciences · 2026Review
- Article
- Dysregulation of phosphatidylethanolamine metabolism associated with upregulation of PNPLA6 in high-fat diet/streptozotocin mice.Frontiers in nutrition · 2026Article
- The cyclic nucleotide binding sites of Swiss-Cheese, thebioRxiv : the preprint server for biology · 2025Article
- Predictive chemoproteomics and functional validation reveal Coeae6g-mediated insecticide cross-resistance in the malaria vector Anopheles gambiae.Nature communications · 2025Article
- PNPLA6 regulates retinal homeostasis by choline through phospholipid turnover.Nature communications · 2025Article
- Review
- Activity-based protein profiling of human andiScience · 2022Article
- The Catalytic Domain of Neuropathy Target Esterase Influences Lipid Droplet Biogenesis and Lipid Metabolism in Human Neuroblastoma Cells.Metabolites · 2022Article
- Lipid Dyshomeostasis and Inherited Cerebellar Ataxia.Molecular neurobiology · 2022Review
- Current Knowledge on Mammalian Phospholipase AMolecules (Basel, Switzerland) · 2022Review
- PNPLA6/NTE, an Evolutionary Conserved Phospholipase Linked to a Group of Complex Human Diseases.Metabolites · 2022Review
- Role of Autophagy in Lysophosphatidylcholine-Induced Apoptosis of Mouse Ovarian Granulosa Cells.International journal of molecular sciences · 2022Article
- Article
- Loss ofInternational journal of molecular sciences · 2021Article
- Updating Phospholipase ABiomolecules · 2020Review
- Interaction of the Lysophospholipase PNPLA7 with Lipid Droplets through the Catalytic Region.Molecules and cells · 2020Article
- Characterization of the Interaction of Neuropathy Target Esterase with the Endoplasmic Reticulum and Lipid Droplets.Biomolecules · 2019Article
- ER responses play a key role in Swiss-Cheese/Neuropathy Target Esterase-associated neurodegeneration.Neurobiology of disease · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Neuropathy target esterase (NTE) is inhibited by several organophosphorus (OP) pesticides, chemical warfare agents, lubricants, and plasticizers, leading to OP-induced delayed neuropathy in people (>30,000 cases of human paralysis) and hens (the best animal model for this demyelinating disease). The active site region of NTE as a recombinant protein preferentially hydrolyzes lysolecithin, suggesting that this enzyme may be a type of lysophospholipase (LysoPLA) with lysolecithin as its physiological substrate. This hypothesis is tested here in mouse brain by replacing the phenyl valerate substrate of the standard NTE assay with lysolecithin for an "NTE-LysoPLA" assay with four important findings. First, NTE-LysoPLA activity, as the NTE activity, is 41-45% lower in Nte-haploinsufficient transgenic mice than in their wild-type littermates. Second, the potency of six delayed neurotoxicants or toxicants as in vitro inhibitors varies from IC50 0.02 to 13,000 nM and is essentially the same for NTE-LysoPLA and NTE (r2 = 0.98). Third, the same six delayed toxicants administered i.p. to mice at multiple doses inhibit brain NTE-LysoPLA and NTE to the same extent (r2 = 0.90). Finally, their in vivo inhibition of brain NTE-LysoPLA generally correlates with delayed toxicity. Therefore, OP-induced delayed toxicity in mice, and possibly the hyperactivity associated with NTE deficiency, may be due to NTE-LysoPLA inhibition, leading to localized accumulation of lysolecithin, a known demyelinating agent and receptor-mediated signal transducer. This mouse model has some features in common with OP-induced delayed neuropathy in hens and people but differs in the neuropathological signs and apparently the requirement for NTE aging.
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