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.
Kong
J
J
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester 01655, USA.
Xu
Z
Z
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000401:mortality; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D016900:Neurofilament Proteins / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics; D016019:Survival Analysis
D016900:Neurofilament Proteins; C044882:neurofilament protein L; C051774:neurofilament protein H; D013482:Superoxide Dismutase