Axonal degeneration as a therapeutic target in the CNS

Paul Lingor, Jan C. Koch, Lars Tönges, Mathias Bähr

Research output: Contribution to journalReview articlepeer-review

95 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)289-311
Number of pages23
JournalCell and Tissue Research
Volume349
Issue number1
DOIs
StatePublished - Jul 2012
Externally publishedYes

Keywords

  • Autophagy
  • Calcium
  • Neurodegeneration
  • Neurotrauma
  • Wallerian degeneration

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