Neurotoxicants and the cytoskeleton

Exposure to occupational and environmental toxicants can result in distal a xonopathies through reaction with various components of the axonal cytoskel eton, The solvents n-hexane and methyl n-butyl ketone are metabolized to th e gamma -diketone, 2,5 -hexanedione, which covalently cross-links neurofila ments, resulting in large paranodal axonal swellings filled with neurofilam ents, Carbon disulfide exposure leads to an identical azonopathy, achieving neurofilament cross-linking through a parallel series of reactions. Acryla mide and ethylene oxide, on the other hand, adduct proteins but do not lead to cross-linking. These toxicants appear to affect the function of microtu bule-associated proteins, such as kinesin, and result in the impaired trans port of synaptic vesicles. Curr Opin Neurol 123733-737. (C) 1999 Lippincott Williams & Wilkins.