The neurodegenerative disease Friedreich's ataxia (FRDA) is the most common autosomal-recessively inherited ataxia and is caused by a GAA triplet repeat expansion in the first intron of the frataxin gene. In this disease, transcription of frataxin, a mitochondrial protein involved in iron homeostasis, is impaired, resulting in a significant reduction in mRNA and protein levels. Global gene expr...

BACKGROUND Friedreich ataxia (FRDA), the most common form of recessive ataxia, is due to reduced levels of frataxin, a highly conserved mitochondrial iron-chaperone involved in iron-sulfur cluster (ISC) biogenesis. Most patients are homozygous for a (GAA)(n) expansion within the first intron of the frataxin gene. A few patients, either with typical or atypical clinical presentation, are compoun...

Friedreich ataxia is an inherited neurodegenerative disease that leads to progressive disability. There is currently no effective treatment and patients die prematurely. The underlying genetic defect leads to reduced expression of the mitochondrial protein frataxin. Frataxin insufficiency causes mitochondrial dysfunction and ultimately cell death, particularly in peripheral sensory ganglia. The...

In eukaryotes, sulfur is mobilized for incorporation into multiple biosynthetic pathways by a cysteine desulfurase complex that consists of a catalytic subunit (NFS1), LYR protein (ISD11), and acyl carrier protein (ACP). This NFS1-ISD11-ACP (SDA) complex forms the core of the iron-sulfur (Fe-S) assembly complex and associates with assembly proteins ISCU2, frataxin (FXN), and ferredoxin to synth...

Defective expression of frataxin is responsible for the inherited, progressive degenerative disease Friedreich's Ataxia (FRDA). There is currently no effective approved treatment for FRDA and patients die prematurely. Defective frataxin expression causes critical metabolic changes, including redox imbalance and ATP deficiency. As these alterations are known to regulate the tyrosine kinase Src, ...

Introduction: Friedreich ataxia (FRDA) is a multi-system autosomal-recessive disease, the most common one of the genetically inherited ataxias. FRDA occurs as a consequence of mutations in the frataxin gene, with an expansion of a GAA trinucleotide. Ataxia with vitamin E deficiency (AVED) is characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich...

OBJECTIVE Gene expression studies in peripheral tissues from patients with neurodegenerative disorders can provide insights into disease pathogenesis, and identify potential biomarkers, an important goal of translational research in neurodegeneration. Friedreich Ataxia (FRDA) is a chronic neurodegenerative disease caused by reduced transcription of frataxin, a ubiquitously expressed protein. We...

Friedreich ataxia is a neurodegenerative disease caused by a GAA triplet repeat expansion in the first intron of the frataxin gene, which results in reduced expression levels of the corresponding protein. Despite numerous animal and cellular models, therapeutic options that mechanistically address impaired frataxin expression are lacking. Here, we have developed a new mammalian cell model emplo...

There is currently no effective treatment for Friedreich's ataxia (FA), the most common of the hereditary ataxias. The disease is caused by mutations in FRDA that drastically reduce expression levels of the mitochondrial protein frataxin. In FA animal models, a key difficulty is obtaining the precise levels of frataxin expression in the appropriate tissues to provoke pathology without early let...