Axonal degeneration as a therapeutic target in the CNS

Cell Tissue Res. 2012 Jul;349(1):289-311. doi: 10.1007/s00441-012-1362-3. Epub 2012 Mar 6.


Degeneration of the axon is an important step in the pathomechanism of traumatic, inflammatory and degenerative neurological diseases. Increasing evidence suggests that axonal degeneration occurs early in the course of these diseases and therefore represents a promising target for future therapeutic strategies. We review the evidence for axonal destruction from pathological findings and animal models with particular emphasis on neurodegenerative and neurotraumatic disorders. We discuss the basic morphological and temporal modalities of axonal degeneration (acute, chronic and focal axonal degeneration and Wallerian degeneration). Based on the mechanistic concepts, we then delineate in detail the major molecular mechanisms that underlie the degenerative cascade, such as calcium influx, axonal transport, protein aggregation and autophagy. We finally concentrate on putative therapeutic targets based on the mechanistic prerequisites.

Publication types

  • Review

MeSH terms

  • Animals
  • Axons / pathology*
  • Central Nervous System / pathology*
  • Central Nervous System Diseases / pathology
  • Central Nervous System Diseases / therapy
  • Humans
  • Models, Biological
  • Nerve Degeneration / pathology*
  • Nerve Degeneration / therapy*