In Friedreich's ataxia, reduction of the mitochondria protein frataxin results in the accumulation of iron and reactive oxygen species, which leads to oxidative damage, neurodegeneration and a diminished lifespan. Recent studies propose that frataxin might play a role in the antioxidative process. Here we show that overexpression of Drosophila frataxin in the mitochondria of female transgenic animals increases antioxidant capability, resistance to oxidative stress insults, and longevity. This suggests that Drosophila frataxin may function to protect the mitochondria from oxidative stresses and the ensuing cellular damage.

Read More: Overexpression of frataxin in the mitochondria increases resistance to oxidative stress and extends lifespan in Drosophila

The inherited ataxias are a large, heterogeneous group of neurodegenerative disorders caused by a variety of gene mutations, the effects of which are exerted through different pathogenic mechanisms. Despite this diversity, oxidative stress seems to be a common factor in the pathogenesis of these disorders, indicating that antioxidants might be potential therapeutics for these currently incurable conditions. Some inherited ataxias, such as ataxia with vitamin E deficiency, are directly caused by defects in small-molecule antioxidants and might be treated by supplying the defective molecule. In most ataxias, however, oxidative stress has more-complex disease-specific causes and consequences, which must be better understood to enable effective treatments to be developed. Results from studies in cellular and animal models need to be brought to the clinic through rigorous trials. The rarity of each of these diseases can, however, make trial design and execution a very difficult task.

Read More: Drug Insight: antioxidant therapy in inherited ataxias

Various pathologies are characterized by the accumulation of toxic iron in cell compartments. In anemia of chronic disease, iron is withheld by macrophages, leaving extracellular fluids iron-depleted. In Friedreich ataxia, iron levels rise in the mitochondria of excitable cells but decrease in the cytosol. We explored the possibility of using deferiprone, a membrane-permeant iron chelator in clinical use, to capture labile iron accumulated in specific organelles of cardiomyocytes and macrophages and convey it to other locations for physiologic reuse. Deferiprone's capacity for shuttling iron between cellular organelles was assessed with organelle-targeted fluorescent iron sensors in conjunction with time-lapse fluorescence microscopy imaging. Deferiprone facilitated transfer of iron from extracellular media into nuclei and mitochondria, from nuclei to mitochondria, from endosomes to nuclei, and from intracellular compartments to extracellular apotransferrin.

Read More: Redistribution of accumulated cell iron: a modality of chelation with therapeutic implications

OBJECTIVE:
Neuropathological descriptions of the brain in Friedreich's ataxia (FRDA) were obtained before availability of the current molecular genetic tests for this disease. Voxel-based morphometry (VBM) enables an unbiased whole-brain quantitative analysis of differences in gray matter (GM) and white matter (WM) volume.

METHODS:
Using VBM, we assessed the brain structural damage in 22 patients with genetically confirmed FRDA and 25 healthy controls. The results were correlated with the disease duration and the severity of the patients' clinical deficits--evaluated using the International Cerebellar Ataxia Rating Scale and Inherited Ataxia Clinical Rating Scale.

Read More: Brain structural damage in Friedreich's ataxia