Murine experimental models of amyotrophic lateral sclerosis: an update

Abstract

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease whose aetiology is unknown. It is characterised by upper and lower motor neuron degeneration. Approximately 90% of cases of ALS are sporadic, whereas the other 10% are familial. Regardless of whether the case is familial o sporadic, patients will develop progressive weakness, muscle atrophy with spasticity, and muscle contractures. Life expectancy of these patients is generally 2 to 5 years after diagnosis.

Development: In vivo models have helped to clarify the aetiology and pathogenesis of ALS, as well as the mechanisms of the disease. However, as these mechanisms are not yet fully understood, experimental models are essential to the continued study of the pathogenesis of ALS, as well as in the search for possible therapeutic targets. Although 90% of cases are sporadic, most of the models used to study ALS pathogenesis are based on genetic mutations associated with the familial form of the disease; the pathogenesis of sporadic ALS remains unknown. Therefore, it would be critical to establish models based on the sporadic form.

Conclusions: This article reviews the main genetic and sporadic experimental models used in the study of this disease, focusing on those that have been developed using rodents.

Keywords: Amyotrophic lateral sclerosis; C9ORF72; Cerebrospinal fluid; Esclerosis lateral amiotrófica; FUS; Líquido cefalorraquídeo; SOD1; TDP43.