Axon Transport and Neuropathy: Relevant Perspectives on the Etiopathogenesis of Familial Dysautonomia

Am J Pathol. 2016 Mar;186(3):489-99. doi: 10.1016/j.ajpath.2015.10.022. Epub 2015 Dec 24.


Peripheral neuropathies are highly prevalent and are most often associated with chronic disease, side effects from chemotherapy, or toxic-metabolic abnormalities. Neuropathies are less commonly caused by genetic mutations, but studies of the normal function of mutated proteins have identified particular vulnerabilities that often implicate mitochondrial dynamics and axon transport mechanisms. Hereditary sensory and autonomic neuropathies are a group of phenotypically related diseases caused by monogenic mutations that primarily affect sympathetic and sensory neurons. Here, I review evidence to indicate that many genetic neuropathies are caused by abnormalities in axon transport. Moreover, in hereditary sensory and autonomic neuropathies. There may be specific convergence on gene mutations that disrupt nerve growth factor signaling, upon which sympathetic and sensory neurons critically depend.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Axonal Transport / genetics*
  • Dysautonomia, Familial / etiology*
  • Dysautonomia, Familial / genetics
  • Dysautonomia, Familial / physiopathology
  • Hereditary Sensory and Autonomic Neuropathies / genetics
  • Hereditary Sensory and Autonomic Neuropathies / physiopathology*
  • Humans
  • Mitochondria / metabolism
  • Mutation
  • Peripheral Nervous System Diseases / genetics
  • Peripheral Nervous System Diseases / physiopathology*
  • Signal Transduction / genetics*