SUPEROXIDE-DISMUTASE AND NEUROFILAMENT TRANSGENIC MODELS OF AMYOTROPHIC-LATERAL-SCLEROSIS

Amyotrophic lateral sclerosis (ALS) is a devastating neurologic diseas e characterized by progressive motor dysfunction that leads to paralys is and eventually death. There are numerous hypotheses for the pathoge nesis of this disease, but the mechanisms of degeneration were difficu lt to investigate before the development of animal models. Transgenic mice with alterations in either the superoxide dismutase (SOD-1) or ne urofilament genes display motor neuron pathology and deficits in motor function and, therefore, provide animal models for the study of ALS n eurodegeneration. Using these animal models, as well as several in vit ro models, researchers have made rapid progress during the last severa l years toward understanding the cause and mechanism of ALS neurodegen eration. These studies have demonstrated that motor neuron degeneratio n in ALS may be secondary to a number of causes, including neurofilame nt disruption, mutations in SOD-1, and glutamate excitotoxicity. Altho ugh each of these mechanisms can cause motor neuron degeneration by it self, studies of transgenic mice have indicated several points at whic h these mechanisms may interact, suggesting that they are components o f one general mechanism of neurodegeneration. J. Exp. Zool. 282:32-47, 1998. (C) 1998 Wiley-Liss, Inc.