Despite advances in the understanding of genetic and molecular aspects of Amyotrophic Lateral Sclerosis (ALS), a rapidly progressive and fatal neurodegenerative disease, the exact pathogenic mechanisms are still largely unknown. For over 20 years, numerous in vitro and in vivo studies have demonstrated the existence of a complex interaction between motor neurons and astrocytes in neurodegeneration. In ALS, astrocytes acquire a reactive phenotype through a phenomenon known as astrogliosis, in which they lose their normal functions and/or acquire highly damaging functions, altering the function and survival of motor neurons. For this review, we set out to analyse the role of astrocytes, particularly in the study of mutations in the SOD1, C9orf72, and TARDBP genes, which are closely related to the pathogenesis of familial ALS. The observations made in this study strongly suggest that the role of astrocytes in ALS is multidimensional, and specifically that astrocytes with different genetic mutations linked to ALS present diverse underlying molecular patterns. Therefore, these cells constitute an extremely promising therapeutic target in the treatment of this neurodegenerative disease.
