The neuroprotective effects of the WldS gene are correlated with proteasome expression rather than apoptosis.
The Wld(s) gene (slow Wallerian degeneration) specifically delays axonal degeneration following injury and in several models of neurodegenerative diseases. It thus provides an interesting tool to study mechanisms of neurodegeneration. We previously crossed the Wld(s) mice with a mouse mutant that has a motoneuron disease (pmn for progressive motor neuronopathy) and showed that the Wld(s) gene prevented axonal loss, increased the life-span and prolonged the survival of the motoneuron cell bodies. In this study we show that spinal motoneurons of pmn/pmn mice, as opposed to axons, die by apoptosis that cannot be prevented by the Wld(s) gene. However, this same gene could partially rescue the proteasome impairment observed in motoneuron cell bodies and axons of pmn/pmn mice. We conclude that the neuroprotective effect of the Wld(s) gene is not related to an inhibition of apoptosis but could possibly be linked to a regulation in proteasome expression.
Simonin
Yannick
Y
Department of Basic Neuroscience, Faculty of Medicine, 1211 Geneva 4, Switzerland.
Ferrer-Alcon
Marcelino
M
Ferri
Anna
A
Kato
Ann C
AC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494827:Bax protein, mouse; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D019253:Proto-Oncogene Proteins c-bcl-2; C442580:Wld protein, mouse; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex