Cytoskeletal Elements in Neurotoxicity*

Toxic Peripheral Neuropathies: Agents and Mechanisms

“…Because the perikaryon is a major source of biosynthesis for components of the axon, there is an essential requirement to distribute these biomolecules that include neurotransmitters, proteins, and organelles along the length of the axon via axonal transport. 62,63 Transport of cargo synthesized within the neuron proceeds along microtubules mediated by the ATP-dependent microtubule motors kinesin and dynein ( Figure 1). 63 These molecules provide mechanochemical force through physical interaction with microtubules and their ATPase activity.…”

“…Chemotherapeutic agents that compromise the dynamics of tubulin elongation and disassembly to disrupt mitotic spindle formation in cancer cells as well as certain environmental chemicals that covalently modify cytoskeletal proteins in a cumulative manner are examples of axonal toxicants that act through this mechanism. 62,64,65 Toxic Disorders of Axons Axonal degeneration is the most commonly observed lesion in toxic peripheral neuropathies. This lesion can be classified as either primary or secondary depending on whether the critical effect is within the axon or another component of the peripheral nervous system, respectively.…”

“…64 Neurofilaments are type IV intermediate filaments that are heteropolymers of noncovalently associated neurofilament protein subunits. 62 The subunits include 3 neurofilament proteins termed low-, medium-, and high-molecular-weight neurofilament protein based on their rates of migration in gel electrophoresis and lengths of their carboxy terminus. Additionally, the filamentous structures also incorporate a internexin and peripherin as additional subunits.…”

“…Because the perikaryon is a major source of biosynthesis for components of the axon, there is an essential requirement to distribute these biomolecules that include neurotransmitters, proteins, and organelles along the length of the axon via axonal transport. 62,63…”

“…Integral to maintaining normal structure and transport functions are the filamentous proteins of the axonal cytoskeleton. 62 These proteins comprise 3 families categorized based upon their size. The smallest microfilaments of assembled actin filaments are located along the periphery of the axoplasm juxtaposed to the axolemma.…”