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.
Highlights
The axon represents the largest functional entity in many neuronal populations, e.g. spanning up to more than onePaul Lingor and Jan C
Following mechanical axonal damage in a crush model of the optic nerve, an increased number of autophagosomes has been observed in the vicinity of the lesion site and this is dependent on calcium influx
Life-imaging techniques (Misgeld and Kerschensteiner 2006) and magnetic resonance imaging (MRI) methods (Ge 2006; Fox et al 2011; Kim et al 2011) might yield more information and further insights can be expected from the evolution of these methods (Westphal et al 2008)
Summary
The axon represents the largest functional entity in many neuronal populations, e.g. spanning up to more than onePaul Lingor and Jan C. Membrane disruption in traumatic brain or spinal cord injury, for example, might eventually result in calcium influx, calpain-mediated cleavage and axonal transport breakdown.
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