Impact of SOD1 Transcript Variants on Amyotrophic Lateral Sclerosis Severity.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that affects motor neurons of people, leading to death. This pathology can be caused by mutations in different genes, including superoxide dismutase 1 (). Previous studies have pointed out the presence of two transcripts of , a short one and a long one. The aim of this study was the investigation of these two transcripts both in the SH-SY5Y cell line and in patients' peripheral blood mononuclear cells. We found that the shortest transcript is upregulated under stress conditions in both the cellular model and the patients' cells. Moreover, we found a potential correlation between the short transcript and the severity of the pathology, which also correlates with the age of patients. No correlation was found between transcripts and the progression of the disease. These data suggest a toxic effect of short transcripts in ALS patients, by affecting the severity of the pathology making it a possible biomarker for this disease. Interestingly, our data suggest that a short transcript does not influence and drive disease progression. The finding of a biomarker will have suitable implications as indicators of disease severity and from the perspective of drug development.