Proteomic analysis unveils Gb3-independent alterations and mitochondrial dysfunction in a gla^-/- zebrafish model of Fabry disease.

ABSTRACT:

Background

Fabry disease (FD) is a rare lysosomal storage disorder caused by mutations in the GLA gene, resulting in reduced or lack of α-galactosidase A activity. This results in the accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in lysosomes causing cellular impairment and organ failures. While current therapies focus on reversing Gb3 accumulation, they do not address the altered cellular signaling in FD. Therefore, this study aims to explore Gb3-independent mechanisms of kidney damage in Fabry disease and identify potential biomarkers.

Methods

To investigate these mechanisms, we utilized a zebrafish (ZF) gla^-/- mutant (MU) model. ZF naturally lack A4GALT gene and, therefore, cannot synthesize Gb3. We obtained kidney samples from both w

SUBMITTER: Elsaid HOA 

PROVIDER: S-EPMC10478213 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature