Molecular Mechanisms and Therapeutics for the GAA·TTC Expansion Disease Friedreich Ataxia.

ABSTRACT: Friedreich ataxia (FRDA), the most common inherited ataxia, is caused by transcriptional silencing of the nuclear FXN gene, encoding the essential mitochondrial protein frataxin. Currently, there is no approved therapy for this fatal disorder. Gene silencing in FRDA is due to hyperexpansion of the triplet repeat sequence GAA·TTC in the first intron of the FXN gene, which results in chromatin histone modifications consistent with heterochromatin formation. Frataxin is involved in mitochondrial iron homeostasis and the assembly and transfer of iron-sulfur clusters to various mitochondrial enzymes and components of the electron transport chain. Frataxin insufficiency leads to progressive spinocerebellar neurodegeneration, causing symptoms of gait and limb ataxia, slurred speech, muscle weakne

SUBMITTER: Gottesfeld JM 

PROVIDER: S-EPMC6985418 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature