Acrylamide-induced nerve terminal damage: Relevance to neurotoxic and neurodegenerative mechanisms

Richard M. LoPachin, Terrence Gavin

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Acrylamide (ACR) has demonstrable neurotoxic effects in animals and humans that stem from its chemical behavior as a soft electrophilic α,β-unsaturated carbonyl compound. Evidence is presented that the nerve terminal is a primary site of ACR action and that inhibition of neurotransmission mediates the development of neurological deficits. At the mechanistic level, recent proteomic, neurochemical, and kinetic data are considered, which suggest that ACR inhibits neurotransmission by disrupting presynaptic nitric oxide (NO) signaling. Nerve-terminal damage likely mediates the neurological complications that accompany the occupational exposure of humans to ACR. In addition, the proposed molecular mechanism of synaptotoxicity has substantial implications for the pathogenesis of Alzheimer's disease and other neurodegenerative conditions that involve neuronal oxidative stress and the secondary endogenous generation of acrolein and other conjugated carbonyl chemicals.

Original languageEnglish (US)
Pages (from-to)5994-6003
Number of pages10
JournalJournal of Agricultural and Food Chemistry
Volume56
Issue number15
DOIs
StatePublished - Aug 13 2008

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Keywords

  • Alzheimer's disease
  • Electrophile
  • Neurodegeneration
  • Spinal cord injury
  • Stroke
  • Toxic neuropathy

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

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