In vitro evidence that covalent crosslinking of neurofilaments occurs in gamma-diketone neuropathy.

Abstract:

: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 axonal swellings observed in DMHD toxicity are in the proximal axon, as seen in intoxication with beta, beta'-iminodipropionitrile, rather than in the distal axon, where neurofilamentous swellings are observed in n-hexane, carbon disulfide, and acrylamide neurotoxicity. In these studies, 14C-labeled DMHD and 2-butanone were synthesized and allowed to react with peripheral nerve. Only 14C-labeled DMHD resulted in stable radiolabeled protein polymers, which were retained by nitrocellulose filters with pore sizes as large as 12 microns. More specific evidence for covalent crosslinking of neurofilaments was obtained when DMHD was allowed to react with peripheral nerve in which the neurofilaments had been pulse-labeled with L-[35S]methionine.

authors

Graham DG,Szakál-Quin G,Priest JW,Anthony DC

doi

10.1073/pnas.81.15.4979

subject

Has Abstract

pub_date

1984-08-01 00:00:00

pages

4979-82

issue

15

eissn

0027-8424

issn

1091-6490

journal_volume

81

pub_type

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