The Role of SOD1 and Oxidative Stress in Amyotrophic Lateral Sclerosis: An Overview
- 1Departamento de Genética, Instituto Nacional de Neurología y Neurocirugía, Mexico City 14269, Mexico
- 2Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City 03104, Mexico
Abstract
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder that selectively affects motor neurons. The median survival time after diagnosis is 2 to 5 years. Oxidative stress (OS), driven mainly by reactive oxygen species (ROS), plays a central role in motor neuron (MN) degeneration. In this narrative review, we analyse the pathogenic role of SOD1 variants and their contribution to OS in ALS. SOD1 mutations alter the Cu/Zn superoxide dismutase enzyme, thereby promoting oxidative damage and triggering neuroinflammatory cascades via the MAPK, NF-κB and Nrf2/ARE signalling pathways. We also discuss emerging proteomic and machine-learning biomarkers, as well as the current therapeutic landscape. Riluzole and edaravone are approved treatments, while AMX0035 was approved in 2022 but withdrawn in 2024. Masitinib and EPI-589 remain investigational. In the realm of genetic therapies, the antisense oligonucleotide tofersen received accelerated FDA approval in 2023 for SOD1-ALS, primarily due to its ability to reduce plasma neurofilament light chain levels. However, the clinical benefit remains modest. RNA interference has reached human trials, while CRISPR/Cas9 remains in the preclinical stage. Both approaches have shown promising results in experimental models. Further research into ALS pathogenesis is needed to develop treatments that integrate antioxidant, anti-inflammatory, and gene-editing strategies.
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BibTeX
@article{gomezperez2026role,
title = {{The Role of SOD1 and Oxidative Stress in Amyotrophic Lateral Sclerosis: An Overview}},
author = {Carlos Alberto Gómez-Pérez and Miguel Ángel Ramírez-García and Petra Yescas-Gómez},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209084},
url = {https://www.mdpi.com/1422-0067/27/20/9084},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Role of SOD1 and Oxidative Stress in Amyotrophic Lateral Sclerosis: An Overview
AU - Carlos Alberto Gómez-Pérez
AU - Miguel Ángel Ramírez-García
AU - Petra Yescas-Gómez
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209084
UR - https://www.mdpi.com/1422-0067/27/20/9084
AB - Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder that selectively affects motor neurons. The median survival time after diagnosis is 2 to 5 years. Oxidative stress (OS), driven mainly by reactive oxygen species (ROS), plays a central role in motor neuron (MN) degeneration. In this narrative review, we analyse the pathogenic role of SOD1 variants and their contribution to OS in ALS. SOD1 mutations alter the Cu/Zn superoxide dismutase enzyme, thereby promoting oxidative damage and triggering neuroinflammatory cascades via the MAPK, NF-κB and Nrf2/ARE signalling pathways. We also discuss emerging proteomic and machine-learning biomarkers, as well as the current therapeutic landscape. Riluzole and edaravone are approved treatments, while AMX0035 was approved in 2022 but withdrawn in 2024. Masitinib and EPI-589 remain investigational. In the realm of genetic therapies, the antisense oligonucleotide tofersen received accelerated FDA approval in 2023 for SOD1-ALS, primarily due to its ability to reduce plasma neurofilament light chain levels. However, the clinical benefit remains modest. RNA interference has reached human trials, while CRISPR/Cas9 remains in the preclinical stage. Both approaches have shown promising results in experimental models. Further research into ALS pathogenesis is needed to develop treatments that integrate antioxidant, anti-inflammatory, and gene-editing strategies.
SN - 1422-0067
ER -