Oxidative Stress and the Homeodynamics of Iron Metabolism

Oxidative Stress and the Homeodynamics of Iron Metabolism. Nikolaus Bresgen and Peter M. Eckl; Biomolecules 2015, 5(2), 808-847; doi:10.3390/biom5020808

In conclusion, cellular iron homeodynamics is based on a well-orchestrated interaction of iron uptake, intracellular transport, iron storage, usage and export, which is embedded in cellular metabolic and surveillance control. Under stress conditions, this orchestration changes in order to maintain homeodynamics and protect the cell from severe destabilization.

Gene Expression Profile in Peripheral Blood Cells of Friedreich Ataxia Patients

Gene Expression Profile in Peripheral Blood Cells of Friedreich Ataxia Patients. Agessandro Abrahao, Jose Luiz Pedroso, Patricia de Carvalho Aguiar and Orlando Barsottini; Neurology April 6, 2015 vol. 84 no. 14 Supplement P2.122

We found a robust downregulation of FXN, but no statistically significant differences were found between FRDA and controls for the remaining genes. Except for FXN, our study did not find a differential gene expression profile in PBCs of FRDA patients and a reliable gene expression profile biomarker obtained from an easily accessible tissue remains unclear.

Clinical Trial: Biomarkers in Friedreich's Ataxia

Clinical Trial: Biomarkers in Friedreich's Ataxia ClinicalTrials.gov Identifier: NCT02497534. First received: July 7, 2015

Sponsor: University of Florida

The purpose of this project is to characterize measures of cardiac performance and neuromuscular physiology in FA patients using novel techniques, including echocardiography and magnetic resonance imaging (MRI), metabolic exercise testing, and neurophysiological outcomes.

This study is not yet open for participant recruitment.

Regional Cerebral Disease Progression in Friedreich's Ataxia: A Longitudinal Diffusion Tensor Imaging Study

Regional Cerebral Disease Progression in Friedreich's Ataxia: A Longitudinal Diffusion Tensor Imaging Study. Mascalchi, M., Toschi, N., Giannelli, M., Ginestroni, A., Della Nave, R., Tessa, C., Piacentini, S., Dotti, M. T., Aiello, M., Nicolai, E., Soricelli, A., Salvi, F. and Diciotti, S., Journal of Neuroimaging.(2015) doi: 10.1111/jon.12270

DTI can track brain microstructural changes in FRDA and can be considered a potential biomarker of disease progression.

Science Heroes: Annalisa Pastore: A love story with the double helix that started at 17

Science Heroes: Annalisa Pastore: A love story with the double helix that started at 17. Frontiers Blog, Posted on July 14, 2015

This led her to—at least partially— identify the role of the protein, resulting from the expression of frataxin, in the disease mechanism. These findings could ultimately open the door to designing a new strategy to treat Friedreich’s ataxia, and other neurodegenerative diseases.

Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism.

Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism. Rikke K. J. Olsen, Nanna Cornelius, and Niels Gregersen; J Inherit Metab Dis. 2015; 38(4): 703–719.
Published online 2015 May 30. doi: 10.1007/s10545-015-9861-5

Springer OPEN Choice

Based on our own and other’s studies we re-introduce the ROS triangle model and discuss how inborn errors of mitochondrial metabolism, by production of pathological amounts of ROS, may cause disturbed redox signalling and induce chronic cell stress with non-resolving or compromised cell repair responses and increased susceptibility to cell stress induced cell death.

TORC1 Inhibition by Rapamycin Promotes Antioxidant Defences in a Drosophila Model of Friedreich’s Ataxia

TORC1 Inhibition by Rapamycin Promotes Antioxidant Defences in a Drosophila Model of Friedreich’s Ataxia. Pablo Calap-Quintana, Sirena Soriano, José Vicente Llorens, Ismael Al-Ramahi, Juan Botas, María Dolores Moltó, María José Martínez-Sebastián; PLoS ONE 10(7): e0132376. doi:10.1371/journal.pone.0132376

OPEN ACCESS

We found that genetic reduction in TOR Complex 1 (TORC1) signalling improves the impaired motor performance phenotype of FRDA model flies. Pharmacologic inhibition of TORC1 signalling by rapamycin also restored this phenotype and increased the lifespan and ATP levels. These results point to the TORC1 pathway as a new potential therapeutic target for FRDA and as a guide to finding new promising molecules for disease treatment.

Familial segmental spinal myoclonus: a rare clinical feature of Friedreich’s ataxia

Familial segmental spinal myoclonus: a rare clinical feature of Friedreich’s ataxia. Rajendra Singh Jain, Sunil Kumar and Shankar Tejwani, SpringerPlus 2015, 4:330 doi:10.1186/s40064-015-1121-5

OPEN ACCESS


Spinal segmental myoclonus (SSM) is a unique and rare manifestation of FRDA. This might be the first case report of SSM in FRDA patient.

Dynamics in the sense of dignity over the course of illness: A longitudinal study into the perspectives of seriously ill patients

Dynamics in the sense of dignity over the course of illness: A longitudinal study into the perspectives of seriously ill patients. Isis E. van Gennip, H. Roeline W. Pasman, Mariska G. Oosterveld-Vlug, Dick L. Willems, Bregje D. Onwuteaka-Philipsen; International Journal of Nursing Studies, Available online 27 June 2015, ISSN 0020-7489, http://dx.doi.org/10.1016/j.ijnurstu.2015.06.010.

Single-molecule spectroscopy of protein conformational dynamics in live eukaryotic cells

Single-molecule spectroscopy of protein conformational dynamics in live eukaryotic cells. Iwo König, Arash Zarrine-Afsar, Mikayel Aznauryan, Andrea Soranno, Bengt Wunderlich, Fabian Dingfelder, Jakob C Stüber, Andreas Plückthun, Daniel Nettels & Benjamin Schuler; Nature Methods (2015)doi:10.1038/nmeth.3475 Published online 06 July 2015

Advances in methodology are making it gradually more feasible to investigate biomolecular processes in their native cellular environment. The ultimate goal is to reach quantitative molecular understanding with the same rigor as in test-tube experiments.The results on protein GB1 and frataxin indicated a remarkable robustness in the conformational stabilities and even folding kinetics of these proteins in cells compared to in simple buffered solutions. We therefore expect that single-molecule spectroscopy will play an important role in bridging the gap between our quantitative understanding of biomolecules in vitro and in vivo.


Source: Single-molecule spectroscopy of protein conformational dynamics in live eukaryotic cells