Friedreich ataxia (FRDA) is due to a triplet repeat expansion in FXN, resulting in deficiency of the mitochondrial protein frataxin. Resveratrol is a naturally occurring polyphenol, identified to increase frataxin expression in cellular and mouse models of FRDA and has anti-oxidant properties. This open-label, non-randomized trial evaluated the effect of two different doses of resveratrol on peripheral blood mononuclear cell (PBMC) frataxin levels over a 12-week period in individuals with FRDA. Secondary outcome measures included PMBC FXN mRNA, oxidative stress markers, and clinical measures of disease severity.
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In this section, you will find the most recent FA research publications, many of which are funded by FARA, as well as information on upcoming conferences and symposiums. You can search for articles by date using the archive box in the right hand column. To locate FARA Funded or Supported Research, click the hyperlink in the right hand column. You may also search for specific content using key words or phrases in the search button at the top right of your screen. Please be sure to visit other key research sections of our website for information on FARA's Grant Program and the Treatment Pipeline.
Iron loading site on the Fe-S cluster assembly scaffold protein is distinct from the active site
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- Category: Funded Research
Iron-sulfur (Fe-S) cluster containing proteins are utilized in almost every biochemical pathway. The unique redox and coordination chemistry associated with the cofactor allows these proteins to participate in a diverse set of reactions, including electron transfer, enzyme catalysis, DNA synthesis and signaling within several pathways. Due to the high reactivity of the metal, it is not surprising that biological Fe-S cluster assembly is tightly regulated within cells. In yeast, the major assembly pathway for Fe-S clusters is the mitochondrial ISC pathway. Yeast Fe-S cluster assembly is accomplished using the scaffold protein (Isu1) as the molecular foundation, with assistance from the cysteine desulfurase (Nfs1) to provide sulfur, the accessory protein (Isd11) to regulate Nfs1 activity, the yeast frataxin homologue (Yfh1) to regulate Nfs1 activity and participate in Isu1 Fe loading possibly as a chaperone, and the ferredoxin (Yah1) to provide reducing equivalents for assembly.
Read More: Iron loading site on the Fe-S cluster assembly scaffold protein is distinct from the active site
Abnormal Cochlear Potentials in Friedreich's Ataxia Point to Disordered Synchrony of Auditory Nerve Fiber Activity
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Selective observation of the disordered import signal of a globular protein by in-cell NMR: The example of frataxins
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- Category: Scientific News
We have exploited the capability of in-cell NMR to selectively observe flexible regions within folded proteins to carry out a comparative study of two members of the highly conserved frataxin family which are found both in prokaryotes and in eukaryotes. They all contain a globular domain which shares more than 50% identity, which in eukaryotes is preceded by an N-terminal tail containing the mitochondrial import signal. We demonstrate that the NMR spectrum of the bacterial ortholog CyaY cannot be observed in the homologous E. coli system, although it becomes fully observable as soon as the cells are lysed. This behavior has been observed for several other compact globular proteins as seems to be the rule rather than the exception. The NMR spectrum of the yeast ortholog Yfh1 contains instead visible signals from the protein.
Sensorimotor skills in Fxn KO/Mck mutants deficient for frataxin in muscle
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Friedreich ataxia is the most common autosomal recessive disorder of the cerebellum, causing degeneration of spinal sensory neurons and spinocerebellar tracts. The disease is caused by severely reduced levels of frataxin, a mitochondrial protein involved in iron metabolism. An experimental model has been generated by crossing mice homozygous for a conditional allele of the Fxn gene with mice heterozygous for a deleted exon 4 of Fxn carrying a tissue-specific Cre transgene under control of the muscle creatine kinase promoter. Relative to wild-type, Fxn null mutants were impaired on tests of motor coordination comprising horizontal bar, vertical pole, and the rotorod as well as displaying gait anomalies and the hindlimb clasping response. The Fxn KO/Mck model reproduces some key features of patients with Friedreich ataxia and provides an opportunity of ameliorating their symptoms with experimental therapies.
Read More: Sensorimotor skills in Fxn KO/Mck mutants deficient for frataxin in muscle
- Excision of expanded GAA repeats alleviates the molecular phenotype of Friedreich's ataxia
- The pathogenesis of cardiomyopathy in friedreich ataxia
- GSK Discovery Fast Track Challenge opening soon
- Ferredoxin, in conjunction with NADPH and ferredoxin-NADP reductase, transfers electrons to the complex IscS/IscU to promote iron-sulfur cluster assembly
- A novel GAA repeat expansion-based mouse model of Friedreich ataxia