title: The neuroprotective factor Wlds does not attenuate mutant SOD1-mediated motor neuron disease.
abstract: Selective degeneration and death of motor neurons in SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS) is accompanied by axonal disorganization and reduced slow axonal transport in the three most frequently used mouse models of mutant SOD1-mediated ALS. To test whether suppression of axonal degeneration (frequently known as Wallerian degeneration) could slow disease development, we took advantage of a spontaneous mouse mutant Wld(s) (Wallerian degeneration slow) in which the programmed axonal degenerative process that is normally activated after axonal injury is significantly delayed. Despite its effectiveness in delaying axonal loss in other neurodegenerative models, the presence of Wld(s) did not slow disease onset, ameliorate mutant motor neuron death, axonal degeneration, or preserve synaptic attachments in mice that develop disease from ALS-linked SOD1 mutants SOD1G37R or SOD1G85R. However, presynaptic endings in both the presence and absence of Wld(s) showed high accumulations of mitochondria and synaptic vesicles, implicating errors of retrograde transport as a consequence of SOD1-mutant damage to axons.
authors.affiliation: Ludwig Institute for Cancer Research and Departments of Medicine and Neuroscience, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Vande Velde
authors.forename: Michael L
authors.initials: ML
authors.lastname: Garcia
authors.forename: Xinghua
authors.initials: X
authors.lastname: Yin
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Trapp
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D019610:Cytoprotection / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D016472:Motor Neuron Disease / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D009046:Motor Neurons / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009469:Neuromuscular Junction / Q000473:pathology / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000473:pathology / Q000648:ultrastructure; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D013572:Synaptic Vesicles / Q000473:pathology / Q000648:ultrastructure; D014855:Wallerian Degeneration / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D009419:Nerve Tissue Proteins; C000606290:SOD1 protein, human; C442580:Wld protein, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1