# Impact of SOD1 Transcript Variants on Amyotrophic Lateral Sclerosis Severity

## TL;DR

This study explores how different versions of the SOD1 gene affect the severity of ALS, finding that a shorter transcript correlates with disease severity but not progression.

## Contribution

The study identifies a potential biomarker for ALS severity through the analysis of SOD1 transcript variants.

## Key findings

- The short SOD1 transcript is upregulated under stress in both cell models and patient cells.
- The short SOD1 transcript correlates with disease severity and patient age but not disease progression.
- The short transcript may act as a toxic factor and potential biomarker for ALS severity.

## Abstract

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 (SOD1). Previous studies have pointed out the presence of two transcripts of SOD1, 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 SOD1 transcript is upregulated under stress conditions in both the cellular model and the patients’ cells. Moreover, we found a potential correlation between the short SOD1 transcript and the severity of the pathology, which also correlates with the age of patients. No correlation was found between SOD1 transcripts and the progression of the disease. These data suggest a toxic effect of short SOD1 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 SOD1 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.