Brain microvascular endothelial cells differentiated from a Friedreich's Ataxia patient iPSC are deficient in tight junction protein expression and paracellularly permeable.

ABSTRACT: Friedreich's Ataxia (FA) is a rare, inherited ataxia resulting from GAA triplet expansions in the first intron of the Frataxin (FXN) gene, which encodes a mitochondrial protein involved in the incorporation of iron into iron-sulfur clusters. We previously identified decreased levels of F-actin and tight junction (TJ) proteins, which coincided with paracellular permeability in an FXN shRNA-mediated knockdown immortalized human brain microvascular endothelial cell (BMVEC) model. This premise is underexplored in the FA literature, prompting us to confirm these findings using a patient-derived iPSC model. One line each of FA patient iPSCs and age- and sex-matched apparently healthy iPSCs were differentiated into BMVEC-like cells. We quantified actin glutathionylation, F-actin abundance,

SUBMITTER: Smith FM 

PROVIDER: S-EPMC12037585 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature