Extra Axonal Neurofilaments Do Not Exacerbate Disease Caused by Mutant Cu,Zn Superoxide Dismutase

Abstract

A recent report by T. L. Williamson et al. (1998, Proc. Natl. Acad. Sci. USA 95, 9631–9636) showed that disease caused by expression of mutant Cu,Zn superoxide dismutase (SOD1) in mice was slowed down by disruption of the neurofilament light (NF-L) gene. This led to the conclusion that decreasing the axonal amount of neurofilaments reduces the vulnerability of motor neurons to toxicity mediated by mutant SOD1. We report here that, unexpectedly, overexpression of human NF-L proteins resulting in extra axonal neurofilaments does not shorten the life span of transgenic mice expressing a mutant SOD1 (SOD1G37R). Microscopic examination of spinal cord and ventral roots even shows modest protective effects of NF-L overexpression. These results suggest that axonal neurofilaments are not an exacerbating factor in motor neuron disease mediated by mutant SOD1 and that perikaryal neurofilaments may even have beneficial effects.

Keywords

• amyotrophic lateral sclerosis
• neurofilament
• Cu,Zn superoxide dismutase (SOD1)
• motor neuron disease
• transgenic mouse model
• neuroprotection