Overexpression of neurofilament subunit NF-L and NF-H extends survival of a mouse model for amyotrophic lateral sclerosis

Mutations in superoxide dismutase 1 (SOD1) cause amyotrophic lateral sclerosis (ALS) in a subset of patients. Neurofilaments (NFs), the most abundant protein in motoneurons, may play a role in motoneuron degeneration. To investigate this role, we crossed transgenic mice expressing SOD1 mutant G93A (G93A mice) with mice overexpressing mouse neurofilament subunit H (H mice) or L (L mice). G93A mice overexpressing either NF-L or NF-H developed ALS later and survived longer than the G93A mice on a wild type background. These results illustrate a beneficial role of neurofilaments in ALS and call into question of several hypotheses regarding the role of neurofilaments in the development of ALS. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.