Axonal transport of neurofilament proteins in IDPN neurotoxicity.
The neurofibrillary changes produced by IDPN are the consequence of the ability of the agent to impair the slow axonal transport of neurofilaments. The susceptibility of various neurons to this effect depends upon their neurofilament content; neurofilament-rich large caliber axons are severely affected. In motor neurons the half-velocities of neurofilament proteins are reduced 2-10 fold, while tubulin and other slow component constituents are only mildly altered. Optic nerve fibers are intermediate in vulnerability, and small neurofilament-poor fibers have little change in slow transport. The agent acts directly on the axon, and the transport defect is expressed all along the course of susceptible axons. Similar alterations in neurofilament transport have recently been found with 3,4-dimethyl-2,5-hexanedione, indicating that similar pathogenetic mechanisms can occur with toxic agents other than IDPN.
J W
JW
Griffin
I
I
Parhad
B
B
Gold
D L
DL
Price
P N
PN
Hoffman
K
K
Fahnestock
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D001369:Axons / Q000378:metabolism; D006588:Hexanones / Q000633:toxicity; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007382:Intermediate Filaments; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D016900:Neurofilament Proteins; D009570:Nitriles / Q000633:toxicity*; D051381:Rats
D006588:Hexanones; D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; D009570:Nitriles; C039195:3,4-dimethyl-2,5-hexanedione; C008110:3,3'-iminodipropionitrile