Neurotoxic probes of the axonal cytoskeleton

Neurofibrillary changes, characterized by accumulations of neurofilaments within the neuronal perikaryon or axon, occur in a variety of human and experimental disorders. The pathogenesis of one model, β,β′-iminodipropionitrile (IDPN) toxicity, is partially understood. IDPN produces a distinctive alteration in which microtubules are segregated from neurofilaments. In this model, the axonal transport of neurofilaments is impaired, resulting in accumulations of neurofilaments in the proximal portions of large axons. Several lines of evidence suggest that similar mechanisms may underlie the neurotoxicity of other agents, including 2,5-hexanedione. These agents represent a distinctive class of toxic probes for studies of cytoskeletal organization and axonal transport.