Acrylamide-induced nerve terminal damage: relevance to neurotoxic and neurodegenerative mechanisms.
Acrylamide (ACR) has demonstrable neurotoxic effects in animals and humans that stem from its chemical behavior as a soft electrophilic alpha,beta-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.
Lopachin
Richard M
RM
Department of Anesthesiology, Albert Einstein College of Medicine, Montefiore Medical Center, 111 East 210th Street, Bronx, New York 10467, USA. lopachin@aecom.yu.edu
Gavin
Terrence
T
D020106:Acrylamide / Q000633:toxicity*; D000475:Alkenes / Q000378:metabolism; D000544:Alzheimer Disease / Q000139:chemically induced; D000818:Animals; D006801:Humans; D009410:Nerve Degeneration / Q000139:chemically induced; D009411:Nerve Endings / Q000187:drug effects*; D009422:Nervous System Diseases / Q000139:chemically induced; D019636:Neurodegenerative Diseases / Q000139:chemically induced*; D009569:Nitric Oxide / Q000378:metabolism; D016273:Occupational Exposure / Q000009:adverse effects
D000475:Alkenes; D020106:Acrylamide; D009569:Nitric Oxide