Neurotoxicants and the cytoskeleton.
Exposure to occupational and environmental toxicants can result in distal axonopathies through reaction with various components of the axonal cytoskeleton. The solvents n-hexane and methyl n-butyl ketone are metabolized to the beta-diketone, 2,5-hexanedione, which covalently cross-links neurofilaments, resulting in large paranodal axonal swellings filled with neurofilaments. Carbon disulfide exposure leads to an identical axonopathy, achieving neurofilament cross-linking through a parallel series of reactions. Acrylamide and ethylene oxide, on the other hand, adduct proteins but do not lead to cross-linking. These toxicants appear to affect the function of microtubule-associated proteins, such as kinesin, and result in the impaired transport of synaptic vesicles.
Graham
D G
DG
Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232-2562, USA. doyle.graham@mcmail.vanderbilt.edu
D001369:Axons / Q000187:drug effects / Q000473:pathology; D003599:Cytoskeleton / Q000187:drug effects*; D006801:Humans; D009498:Neurotoxins / Q000633:toxicity*
D009498:Neurotoxins