Disease mechanisms in inherited neuropathies

Inherited neuropathies are caused by dominant or recessive mutations in genes that are expressed by neurons and/ or Schwann cells. In demyelinating neuropathies, the deleterious effects originate primarily in myelinating Schwann cells. In axonal neuropathies, neurons ( axons) are initially affected. In demyelinating neuropathies, the axonal cytoskeleton is altered and axonal transport is disrupted. In some axonal neuropathies, genes that are directly involved in axonal transport are mutated. So, a common consequence of inherited neuropathies is disruption of the ability of neurons to transport cargo efficiently along the entire length of their axons. These findings correlate with the observations that axonal atrophy and/ or loss are primarily responsible for the clinical disability in hereditary neuropathies.