# Fabry Disease: A Focus on the Role of Oxidative Stress

## TL;DR

Fabry disease causes oxidative stress through Gb3 accumulation, leading to organ damage and highlighting the need for antioxidant therapies.

## Contribution

This review synthesizes molecular mechanisms of oxidative stress and identifies potential therapeutic strategies in Fabry disease.

## Key findings

- Gb3 accumulation disrupts mitochondrial function and activates pathways that produce reactive oxygen species.
- Biomarkers like malondialdehyde and glutathione status help assess oxidative burden in Fabry disease.
- Oxidative stress contributes to injury in cardiovascular, renal, and nervous systems in Fabry disease.

## Abstract

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency, accumulation of globotriaosylceramide (Gb3), and progressive multiorgan involvement. Increasing evidence indicates that oxidative stress plays a central role in disease pathogenesis. This review aims to synthesize current knowledge on the molecular mechanisms underlying oxidative stress, the relevance of oxidative damage biomarkers, and potential therapeutic implications. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar using terms related to Fabry disease, Gb3 metabolism, mitochondrial and endothelial dysfunction, inflammatory signaling, and oxidative stress markers. Clinical, experimental, and translational studies were included. Available data demonstrate that Gb3 accumulation disrupts mitochondrial function and activates NADPH oxidase, NF-κB, and MAPK signaling pathways, resulting in excessive production of reactive oxygen species. These processes contribute to cellular injury, particularly within the cardiovascular, renal, and nervous systems. Biomarkers such as malondialdehyde, 8-hydroxy-2′-deoxyguanosine, glutathione redox status, and antioxidant enzyme activities appear useful for assessing oxidative burden and monitoring therapeutic responses. Overall, current evidence underscores the pivotal role of oxidative stress in the progression of Fabry disease and highlights the need for further research into targeted antioxidant and disease-modifying therapeutic strategies.