Translational Research on Amyotrophic Lateral Sclerosis (ALS): The Preclinical SOD1 Mouse Model

Maria Mina, Eleni Konsolaki an

Abstract

Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease and is clinically defined by the degeneration of upper and lower motor neurons, leading to paralysis and premature death. 10% of ALS patients suffer from the familial form of the disease and research has revealed a number of responsible mutations in specific genes and loci. Transgenic mouse models carrying human ALS related mutations have been generated for the study of the mechanisms involved in the disease pathogenesis and putative therapies. Mutations in the Cu/ Zn superoxide dismutase 1 (SOD1) gene, accounting for 20% of fALS and up to 5% of sALS, were the first identified to be involved in the disease. In this review, we focus on the first transgenic model used, the SOD1 mouse, which recapitulates many symptoms of the human ALS pathology. SOD1 mouse models have been extensively studied in basic and translational research, in order to unravel the underlying mechanisms, the early signs of the disorder and potential therapeutic interventions. In basic research this model has provided valuable information about ALS causes and progression. In translational research, encouraging results have emerged, but the need for better design of clinical trials is evident. This review presents the impact of the SOD1 mouse models in ALS investigation.