Acrylamide-Induced Nerve Terminal Damage: Relevance to Neurotoxic and Neurodegenerative Mechanisms
- 15 July 2008
- journal article
- review article
- Published by American Chemical Society (ACS) in Journal of Agricultural and Food Chemistry
- Vol. 56 (15), 5994-6003
- https://doi.org/10.1021/jf703745t
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.This publication has 98 references indexed in Scilit:
- Pathways towards and away from Alzheimer's diseaseNature, 2004
- cGMP and S-nitrosylation: two routes for modulation of neuronal excitability by NOTrends in Neurosciences, 2002
- Protein‐Bound AcroleinJournal of Neurochemistry, 1999
- Amyloid‐β Deposition in Alzheimer Transgenic Mice Is Associated with Oxidative StressJournal of Neurochemistry, 1998
- Impairment of Glucose and Glutamate Transport and Induction of Mitochondrial Oxidative Stress and Dysfunction in Synaptosomes by Amyloid β‐Peptide: Role of the Lipid Peroxidation Product 4‐HydroxynonenalJournal of Neurochemistry, 1997
- Redox state, NMDA receptors and NO-related species: Different combinations of heteromeric subunits of the same receptor can yield disparate resultsTrends in Pharmacological Sciences, 1996
- Effects of acrylamide on cotransmission in perivascular sympathetic and sensory nervesJournal of the Autonomic Nervous System, 1994
- Neurotoxicity of glycidamide, an acrylamide metabolite, following intraperitoneal injections in ratsJournal of Toxicology and Environmental Health, 1993
- The effects of acetaldehyde and acrolein on blood pressure in guanethidine-pretreated hypertensive ratsToxicology and Applied Pharmacology, 1983
- Ultrastructural studies of the dying-back process II. The sequestration and removal by Schwann cells and oligodendrocytes of organelles from normal and diseased axonsJournal of Neurocytology, 1974