G Szakál-Quin

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We have postulated that the toxic neuropathies associated with neurofilament-filled axonal swellings have a common pathogenesis, the covalent crosslinking of neurofilaments during anterograde transport. The newly described gamma-diketone, 3,4-dimethyl-2,5-hexanedione (DMHD), is a more potent analogue of the toxic metabolite of n-hexane, 2,5-hexanedione. The(More)
Previous studies from this laboratory have demonstrated that the addition of methyl groups at the 3 and 4 positions of the 2,5-hexanedione (2,5-HD) molecule results both in more rapid pyrrole formation and in enhanced neurotoxicity. In order to define more clearly the relationship between rates of pyrrole formation and neurotoxicity, the dl and meso(More)
The molecular pathogenesis of n-hexane neurotoxicity has been postulated to proceed as follows: The gamma-diketone metabolite, 2,5-hexanedione (HD), reacts with lysyl-amino groups on neurofilaments to form imines. The imines cyclize to form pyrroles. The pyrroles autoxidize, resulting in covalent protein-protein crosslinking within or between(More)
These studies test the hypothesis that in n-hexane neuropathy the gamma-diketone metabolite 2,5-hexanedione (2,5-HD) results in covalent crosslinking of neurofilaments via nucleophilic attack on oxidized pyrrole rings formed from the reaction of 2,5-HD with epsilon-amino groups of lysyl residues. The 2,5-HD analogue and(More)
The neurotoxicity of the dl and meso diastereomers of the gamma-diketone 3,4-dimethyl-2,5-hexanedione (DMHD) was studied to determine if the difference in rates of pyrrole derivatization would influence the clinical and morphological appearance of the neuropathy associated with these gamma-diketones. Two groups of rats received 0.2 mmol/kg/day(More)
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