Most researchers consider that Frataxin plays a role in iron-sulfur cluster biosynthesis because decreased activities of iron-sulfur containing proteins have been reported. Many studies in frataxin function arise from experiments performed with Saccharomyces cerevisiae, as frataxin and the yeast homologue Yfh1 are orthologues. In this work we analyzed the proteome of the yeast model of Friedreich Ataxia. The strategy used was based on the use of two-dimensional electrophoresis and subsequent identification of proteins differentially expressed in deltayfh1 cells by peptide mass fingerprinting. We found that these cells show an increased amount of proteins involved in the oxidative stress response, among them, Superoxide dismutase 1 and 2. However, these two enzymes showed decreased activity in deltayfh1 cells. In the case of superoxide dismutase manganese-dependent (Mn-SOD), this paradox was due to a deficiency in the cellular amount of manganese, because in cells grown in manganese-supplemented media, both Mn-SOD activity was restored. The activities of four Fe-S enzymes were analyzed for the effects of manganese supplementation. Enzyme activities were recovered by manganese treatment, except for aconitase, suggesting that frataxin is not essential for Fe-S clusters biosynthesis. We also analyzed oxidative damage to proteins in cells deficient in YFH1. Iron toxicity is related to its ability to trigger the generation of reactive oxygen species (ROS). These species are highly reactive and have the potential to damage cellular components. By carbonyl group nmunodetection we identified 14 proteins selectively oxidized, most of which showed binding sites to magnesium or nucleotides. In vitro studies showed that oxidation of these proteins can be prevented with magnesium, and increased by ATP. In addition, cheatable iron was found seven times increased in deltayfh1 cells. The use of a chelating agent, was able to prevent inactivation of magnesium dependent enzymes. Superoxide dismutase 1 (CuZn-SOD) was one of the oxidized proteins. This protein was partiality inactive. The relationship between low SOD activity, the high cheatable iron content and protein oxidation was studied in more detail. The addition of copper and manganese to the culture medium prevented both oxidative damage and inactivation of specific proteins. The mutant deficient in SOD1 showed high levels of chelatable iron and inactivation of magnesium-binding enzymes. These facts indicate that the absence of CuZn-SOD activity is the responsible for the high levels of chelatable iron that can cause oxidative damage to proteins in deltayfh1 cells.

The legacy of Marie Schlau: literature to help cure Friedreich's Ataxia

If you feel like reading an unputdownable novel while collaborating with a just and solidary cause, "The Legacy of Marie Schlau" is your book! 100% of all funds raised will be dedicated to medical research to find a cure for Friedreich's Ataxia, a neurodegenerative disease that affects mostly young people, shortening their life expectancy and confining them to a wheelchair.

The life of Marie Schlau, a German Jewish girl born in 1833 hides great unsolved mysteries: accidents, disappearances, enigmas, unknown diagnoses, disturbing murders, love, tenderness, greed, lies, death ... alternatively a different story unfolds every time and takes us closer to the present. Thus, there are two parallel stories unravelling, each in a different age and place, which surprisingly converge in a revelatory chapter.

Paperback and Kindle versions for "The legacy of Marie Schlau" available for sale at Amazon now!


Research projects currently being financed by BabelFAmily

Currently, BabelFAmily is financing two promising research projects aimed at finding a cure for Friedreich's Ataxia. Whenever you make a donation to us or purchase a copy of "The legacy of Marie Schlau", this is where all funds raised will be devoted to:

1) Gene Therapy for Friedreich's Ataxia research project:

The project is the result of an initiative of Spanish people affected by this rare disease who are grouped in GENEFA in collaboration with the Spanish Federation of Ataxias and the BabelFAmily. The Friedreich’s Ataxia Research Alliance (FARA), one of the main patients’ associations in the United States now joins the endeavour.

2) Frataxin delivery research project:
The associations of patients and families Babel Family and the Asociación Granadina de la Ataxia de Friedreich (ASOGAF) channel 80,000 euros of their donations (50% from each organisation) into a new 18-month project at the Institute for Research in Biomedicine (IRB Barcelona). The project specifically aims to complete a step necessary in order to move towards a future frataxin replacement therapy for the brain, where the reduction of this protein causes the most damage in patients with Friedreich’s Ataxia.

The study is headed by Ernest Giralt, head of the Peptides and Proteins Lab, who has many years of experience and is a recognised expert in peptide chemistry and new systems of through which to delivery drugs to the brain, such as peptide shuttles—molecules that have the capacity to carry the drug across the barrier that surrounds and protects the brain. Since the lab started its relation with these patients’ associations in 2013*, it has been developing another two projects into Friedrich’s Ataxia.



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