The Wlds 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 Wlds mice with a mouse mutant that has a motoneuron disease (pmn for progressive motor neuronopathy) and showed that the Wlds 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 Wlds 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 Wlds gene is not related to an inhibition of apoptosis but could possibly be linked to a regulation in proteasome expression.