| Summary: | Fabry disease (FD) is an X-linked lysosomal storage disease, caused by mutations in the <i>GLA</i> gene on the X chromosome, resulting in a deficiency of the lysosomal enzyme α-GAL. This leads to the progressive accumulation of Gb3 in cells, causing multi-systemic effects. FD has been classified as a subgroup of autoinflammatory diseases. NF-κB is a family of ubiquitous and inducible transcription factors that play critical roles in inflammation, in which the p65/p50 heterodimer is the most abundant. The glucocorticoid receptor (GR) represents the physiological antagonists in the inflammation process. A novel spliced variant of p65, named p65 iso5, which can bind the dexamethasone, enhancing GR activity, has been found. This study investigates the potential role of p65 iso5 in the inflammation of subjects with FD. We evaluated in peripheral blood mononuclear cells (PBMCs), from over 100 FD patients, the p65 iso5 mRNA level, and the protein expression. The results showed significantly lower p65 iso5 mRNA and protein expression levels compared to controls. These findings, along with the ability of p65 iso5 to bind dexamethasone and the regulation of the glucocorticoid response in the opposite way of p65, strongly suggest the involvement of p65 iso5 in the inflammatory response in FD.
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