Axon pathology in neurological disease: a neglected therapeutic target.
In the C57BL/Wld(S) mouse, a dominant mutation dramatically delays Wallerian degeneration in injury and disease, possibly by influencing multi-ubiquitination. Studies on this mouse show that axons and synapses degenerate by active and regulated mechanisms that are akin to apoptosis. Axon loss contributes to neurological symptoms in disorders as diverse as multiple sclerosis, stroke, traumatic brain and spinal cord injury, peripheral neuropathies and chronic neurodegenerative diseases, but it has been largely neglected in neuroprotective strategies. Defects in axonal transport, myelination or oxygenation could trigger such mechanisms of active axon degeneration. Understanding how these diverse insults might initiate an axon-degeneration process could lead to new therapeutic interventions.
Coleman
Michael P
MP
Center for Molecular Medicine (ZMMK) and Institute for Genetics, University of Cologne, Zuelpicher Strasse 47, Germany. Michael.Coleman@uni-koeln.de
Perry
V Hugh
VH
D000818:Animals; D001369:Axons / Q000473:pathology* / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D009410:Nerve Degeneration / Q000235:genetics / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009422:Nervous System Diseases / Q000473:pathology* / Q000628:therapy; D046988:Proteasome Endopeptidase Complex; D025801:Ubiquitin / Q000378:metabolism
D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D025801:Ubiquitin; C442580:Wld protein, mouse; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex