Neuropathy Target Esterase as a Biomarker and Biosensor of Delayed Neuropathic Agents

Rudy J. Richardson, R. Mark Worden, Sanjeeva J. Wijeyesakere, Nichole D. Hein, John K. Fink, Galina F. Makhaeva

    Research output: Chapter in Book/Report/Conference proceedingChapter

    • 3 Citations

    Abstract

    Delayed neuropathic (DN) agents are defined here as organophosphorus (OP) compounds that produce OP compound-induced delayed neurotoxicity (OPIDN). This syndrome involves distal sensorimotor degeneration of long, large-diameter axons in peripheral nerves and spinal cord with associated sensory deficits and paralysis typically occurring within 1-4 weeks after exposure. Mechanistic studies indicate that inhibition and aging of more than 70% of neuropathy target esterase (NTE) in neural tissue correlates with development of OPIDN and that acetylcholinesterase (AChE) is not involved. The neuropathic potential of an OP compound can be assessed by its relative inhibitory potency (RIP) against AChE versus NTE. By the convention used in this chapter, a high RIP value indicates that the compound will produce cholinergic toxicity rather than OPIDN. Lymphocyte and platelet NTE can be used as biomarkers of exposure to DN compounds, and human recombinant NTE esterase domain (NEST) has been incorporated into a biosensor for these agents.

    Original languageEnglish (US)
    Title of host publicationHandbook of Toxicology of Chemical Warfare Agents: Second Edition
    PublisherElsevier Inc.
    Pages935-952
    Number of pages18
    ISBN (Print)9780128001592
    DOIs
    StatePublished - Jan 21 2015

    Profile

    Biosensing Techniques
    Esterases
    Biological Markers
    Organophosphorus Compounds
    Acetylcholinesterase
    Peripheral Nerves
    Paralysis
    Cholinergic Agents
    Axons
    Spinal Cord
    Blood Platelets
    Lymphocytes

    Keywords

    • Acetylcholinesterase (AChE)
    • Biosensors
    • Chemical warfare agents
    • Delayed neuropathic agents
    • Irreversible inhibition of esterases
    • Kinetics
    • Neuropathy target esterase (NTE)
    • Organophosphorus compound-induced delayed neuropathy (OPIDN)

    ASJC Scopus subject areas

    • Medicine(all)

    Cite this

    Richardson, R. J., Mark Worden, R., Wijeyesakere, S. J., Hein, N. D., Fink, J. K., & Makhaeva, G. F. (2015). Neuropathy Target Esterase as a Biomarker and Biosensor of Delayed Neuropathic Agents. In Handbook of Toxicology of Chemical Warfare Agents: Second Edition (pp. 935-952). Elsevier Inc.. DOI: 10.1016/B978-0-12-800159-2.00063-4

    Neuropathy Target Esterase as a Biomarker and Biosensor of Delayed Neuropathic Agents. / Richardson, Rudy J.; Mark Worden, R.; Wijeyesakere, Sanjeeva J.; Hein, Nichole D.; Fink, John K.; Makhaeva, Galina F.

    Handbook of Toxicology of Chemical Warfare Agents: Second Edition. Elsevier Inc., 2015. p. 935-952.

    Research output: Chapter in Book/Report/Conference proceedingChapter

    Richardson, RJ, Mark Worden, R, Wijeyesakere, SJ, Hein, ND, Fink, JK & Makhaeva, GF 2015, Neuropathy Target Esterase as a Biomarker and Biosensor of Delayed Neuropathic Agents. in Handbook of Toxicology of Chemical Warfare Agents: Second Edition. Elsevier Inc., pp. 935-952. DOI: 10.1016/B978-0-12-800159-2.00063-4
    Richardson RJ, Mark Worden R, Wijeyesakere SJ, Hein ND, Fink JK, Makhaeva GF. Neuropathy Target Esterase as a Biomarker and Biosensor of Delayed Neuropathic Agents. In Handbook of Toxicology of Chemical Warfare Agents: Second Edition. Elsevier Inc.2015. p. 935-952. Available from, DOI: 10.1016/B978-0-12-800159-2.00063-4

    Richardson, Rudy J.; Mark Worden, R.; Wijeyesakere, Sanjeeva J.; Hein, Nichole D.; Fink, John K.; Makhaeva, Galina F. / Neuropathy Target Esterase as a Biomarker and Biosensor of Delayed Neuropathic Agents.

    Handbook of Toxicology of Chemical Warfare Agents: Second Edition. Elsevier Inc., 2015. p. 935-952.

    Research output: Chapter in Book/Report/Conference proceedingChapter

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