The loss of frataxin in patients results in iron sulfur cluster deficiency and iron accumulation in the mitochondria, making FRDA a fatal and debilitating condition.
To assess with magnetoencephalography the developmental vs progressive character of the impairment of spinocortical proprioceptive pathways in Friedreich ataxia (FRDA).
In addition, GRP75 overexpression rescues frataxin deficiency and abnormal cellular phenotypes such as the abnormal mitochondrial network and decreased ATP levels in FRDA patient-derived cells.
Friedreich's ataxia (FRDA) is a progressive disease affecting multiple organs that is caused by systemic insufficiency of the mitochondrial protein frataxin.
Together, these results provide mechanistic insights into the allosteric-activator role of FXN and suggest new strategies to replace FXN function in the treatment of FRDA.
Numerous approaches are being taken to find a treatment for FRDA, including excision or correction of the repeats by genome engineering methods, gene activation with small molecules or artificial transcription factors, delivery of frataxin to affected cells by protein replacement therapy, gene therapy, or small molecules to increase frataxin protein levels, and therapies aimed at countering the cellular consequences of reduced frataxin.
This review describes the substantial contribution of <i>Drosophila</i> to FRDA research since the characterization of the fly frataxin ortholog more than 15 years ago.
We found that p38 phosphorylation, indicating activation of the p38 pathway, is higher in FRDA cells than in normal control cells, and that siRNA knockdown of frataxin in normal fibroblasts also increases p38 phosphorylation.
The identification of a core set of proteins changing in the FRDA pathogenesis is a useful tool in trying to decipher the function(s) of frataxin in order to clarify the mitochondrial metabolic disease process.
Molecular dynamics simulations are used to elucidate the structure and thermodynamics of DNA triplexes associated with the neurodegenerative disease Friedreich's ataxia (FRDA), as well as complexes of these triplexes with the small molecule netropsin, which is known to destabilise triplexes.
We first showed that diazoxide increases frataxin protein levels in FRDA lymphoblastoid cell lines, via the mammalian target of rapamycin (mTOR) pathway.
We investigated the effects of FRDA on regional long axis function of the left and right ventricles, and also the relationship of long axis systolic (s`) and early diastolic (e`) peak velocities with GAA repeat number on the shorter (GAA1) and longer FXN alleles (GAA2).
Friedreich's ataxia (FRDA) is a progressive neurodegenerative disease that is linked to transcriptional repression of the nuclear FXN gene encoding the essential mitochondrial protein frataxin (FXN).
The effects of stably transfected FAST-1 expression on CTCF occupancy and heterochromatin formation at the FXN locus suggest a direct role for FAST-1 in the FRDA molecular disease mechanism.
Thus, we have analyzed the effects of frataxin knockdown on mitochondrial morphology, mitophagy and ER function in our fly FRDA model using different histological and molecular markers such as tetramethylrhodamine, ethyl ester (TMRE), mitochondria-targeted GFP (mitoGFP), p62, ATG8a, LAMP1, Xbp1 and BiP/GRP78.
FRDA is a rare genetic neurodegenerative disease that involves the partial silencing of frataxin, a small mitochondrial protein that was completely overlooked before being linked to FRDA.
This permitted selection of 3 plTALE<sub>VP64s</sub> and 2 plTALE<sub>SunTag</sub> that increased FXN gene expression by up to 19-fold in different Friedreich ataxia (FRDA) primary fibroblasts.