Diverse cellular and molecular modes of axon degeneration

Trends Cell Biol. 2014 Sep;24(9):515-23. doi: 10.1016/j.tcb.2014.04.003. Epub 2014 Apr 27.


The elimination of large portions of axons is a widespread event in the developing and diseased nervous system. Subsets of axons are selectively destroyed to help fine-tune neural circuit connectivity during development. Axonal degeneration is also an early feature of nearly all neurodegenerative diseases, occurs after most neural injuries, and is a primary driver of functional impairment in patients. In this review we discuss the diversity of cellular mechanisms by which axons degenerate. Initial molecular characterization highlights some similarities in their execution but also argues that unique genetic programs modulate each mode of degeneration. Defining these pathways rigorously will provide new targets for therapeutic intervention after neural injury or in neurodegenerative disease.

Keywords: Wallerian degeneration; axon degeneration; axon retraction; axosome shedding; glia; pruning.

Publication types

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

MeSH terms

  • Axons / metabolism*
  • Axons / pathology
  • Humans
  • Nerve Degeneration / pathology
  • Nervous System / metabolism
  • Nervous System / pathology
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Neuroglia / metabolism*
  • Neuroglia / pathology