title: Axonal degeneration as a therapeutic target in the CNS.
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.
authors.affiliation: Department of Neurology, University Medicine Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany. plingor@gwdg.de
authors.forename: Paul
authors.initials: P
authors.lastname: Lingor
authors.forename: Jan C
authors.initials: JC
authors.lastname: Koch
authors.forename: Lars
authors.initials: L
authors.lastname: Tönges
authors.forename: Mathias
authors.initials: M
authors.lastname: Bähr
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D002490:Central Nervous System / Q000473:pathology*; D002493:Central Nervous System Diseases / Q000473:pathology / Q000628:therapy; D006801:Humans; D008954:Models, Biological; D009410:Nerve Degeneration / Q000473:pathology* / Q000628:therapy*