PMID: 2118823Jun 11, 1990Paper

Giant axonopathy characterized by intermediate location of axonal enlargements and acceleration of neurofilament transport

Brain Research
S MonacoL M Sayre

Abstract

It has previously been shown that 2,5-hexanedione (2,5-HD) and its 3,4-dimethyl derivative (3,4-DMHD) induce neurofilamentous accumulations at prenodal sites in distal and proximal, respectively, regions of peripheral axons. For 2,5-HD, neurofilament (NF) transport is accelerated and this is thought to be directly related to the appearance of the axonal enlargements. For 3,4-DMHD, however, the rate of NF transport cannot be assessed owing to the very proximal position of NF accumulation. In the present study, it is shown that administration to rats of 3-methyl-2,5-hexanedione, the structural 'average' of 2,5-HD and 3,4-DMHD, induces NF accumulations at midway axonal positions of the sciatic and optic systems, and results in acceleration of NF in the sections of optic axons proximal to the enlargements. These results suggest that a common mechanism underlies all gamma-diketone neuropathies, and that the proximodistal pattern of axonal enlargements represents pharmacokinetic variables rather than differences in mode of action. The neurotoxicity of gamma-diketones probably arises from pyrrolation of lysine epsilon-amino groups in crucial regions of NF or related proteins responsible for maintaining the proper supramolecular organi...Continue Reading

References

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Citations

Jan 1, 1993·Molecular Neurobiology·L C Doering
Mar 11, 2005·Acta Neuropathologica·D D Tshala-KatumbayP S Spencer
Feb 1, 1992·Current Opinion in Cell Biology·R A Nixon
Aug 14, 1998·Journal of the Neurological Sciences·A MalandriniA Federico
Sep 13, 2002·Neurotoxicology·Dale W SicklesMarvin A Friedman
Jun 27, 2009·Journal of Toxicology and Environmental Health. Part a·Anthony P DeCaprioRichard M LoPachin
Dec 1, 1993·Neuropathology and Applied Neurobiology·M MorbinN Rizzuto
Feb 17, 2005·Neurotoxicology·Richard M LoPachinMaria L Reid
Aug 4, 2004·Toxicology and Applied Pharmacology·Richard M LoPachin, Anthony P DeCaprio
May 23, 2002·International Journal of Hygiene and Environmental Health·Peter S SpencerMohammad I Sabri
Jan 1, 1995·Critical Reviews in Toxicology·D G GrahamD C Anthony
Jun 23, 2004·Toxicology and Applied Pharmacology·Richard M LoPachinLisa A Opanashuk

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