Cellular, Molecular and Functional Characterisation of YAC Transgenic Mouse Models of Friedreich Ataxia

Cellular, Molecular and Functional Characterisation of YAC Transgenic Mouse Models of Friedreich Ataxia .Anjomani Virmouni S, Sandi C, Al-Mahdawi S, Pook MA; PLoS ONE 9(9): e107416. doi:10.1371/journal.pone.0107416

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Screening for E3-Ubiquitin ligase inhibitors: challenges and opportunities

Screening for E3-Ubiquitin ligase inhibitors: challenges and opportunities. Vivien Landré, Barak Rotblat, Sonia Melino, Francesca Bernassola and Gerry Melino; Oncotarget, Published: September 03, 2014, Advance Publications

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Another interesting approach to inhibit ubiquitination of a specific substrate is to block the ubiquitination of the target rather than blocking the E3 ligase and therefore the ubiquitination of all its targets. This was demonstrated by a study that identified an inhibitor of the ubiquitination of frataxin, a mitochondrial protein whose downregulation is linked to Friedreich’s ataxia, a neuro-and cardiodegenerative disorder. Lavecchia et al.identified the ubiquitination site on frataxin and modelled the position of ubiquitin on the protein surface using in silico docking programs. Next, they used structure based virtual screening coupled with a cell-based assay of the 13 top hits, and identified a small molecule that disrupts the frataxin-ubiquitin interactions and thereby inhibits frataxin ubiquitination.

Edison's orphan drug (EPI-743) misses the mark in Phase II (Rett syndrome)

Edison's orphan drug (EPI-743) misses the mark in Phase II (Rett syndrome). FierceBiotech (Daily Biotech Industry Newsletter), September 4, 2014

Despite the setback, the biotech is still chugging along with mid-stage studies to chart EPI-743's potential in its lead indications, the rare CNS ailments Friedreich's ataxia and Leigh syndrome.

Muscle synergy stability and human balance maintenance

Muscle synergy stability and human balance maintenance. Tytus Wojtara, Fady Alnajjar, Shingo Shimoda and Hidenori Kimura; Journal of NeuroEngineering and Rehabilitation 2014, 11:129 doi:10.1186/1743-0003-11-129 Published: 30 August 2014

These results suggest that SSI can be used to quantitatively evaluate balance maintenance ability.

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Friedreich ataxia: New findings, new challenges

Friedreich ataxia: New findings, new challenges. David R. Lynch M.D., PhD and Lauren Seyer MS; Annals of Neurology, Accepted manuscript online: 27 AUG 2014 01:36AM EST | DOI: 10.1002/ana.24259

Scientists map the ‘editing marks’ on fly, worm, human genomes

Scientists map the ‘editing marks’ on fly, worm, human genomes. By Diana Lutz, NEWSROOM, Washington University in St. Louis. August 28, 2014

Comprehensive maps of these marks will allow them to test ways to safely restore marks altered by human disease

Epigenetic therapy for Friedreich's ataxia

Epigenetic therapy for Friedreich's ataxia;Elisabetta Soragni PhD, Wenyan Miao PhD, Marco Iudicello MD, David Jacoby MD, Stefania Demercanti M, Marinella Clerico MD, Filomena Longo MD, Antonio Piga MD, Sherman Ku PhD, Erica Campau BS, Jintang Du PhD, Pablo Penalver PhD1, Myriam Rai PhD Joseph C. Madara PhD, Kristopher Nazor PhD, Melinda O'Connor PhD, Anton Maximov PhD, Jeanne F. Loring PhD, Massimo Pandolfo MD, Luca Durelli MD, Joel M. Gottesfeld PhD and James R. Rusche PhD. Annals of Neurology, Accepted manuscript online: 27 AUG 2014 04:31AM EST | DOI: 10.1002/ana.24260

Processing of double-R-loops in (CAG)·(CTG) and C9orf72 (GGGGCC)·(GGCCCC) repeats causes instability.

Processing of double-R-loops in (CAG)·(CTG) and C9orf72 (GGGGCC)·(GGCCCC) repeats causes instability. Kaalak Reddy, Monika H.M. Schmidt, Jaimie M. Geist, Neha P. Thakkar, Gagan B. Panigrahi, Yuh-Hwa Wang and Christopher E. Pearson; Nucl. Acids Res. (2014) doi: 10.1093/nar/gku658 First published online: August 21, 2014

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R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X and Friedreich's ataxia.

Cerebellum involvement in cortical sensorimotor circuits for the control of voluntary movements

Cerebellum involvement in cortical sensorimotor circuits for the control of voluntary movements. Rémi D Proville, Maria Spolidoro, Nicolas Guyon, Guillaume P Dugué, Fekrije Selimi, Philippe Isope, Daniela Popa & Clément Léna; Nature Neuroscience 17, 1233–1239 (2014) doi:10.1038/nn.3773

Towards Understanding RNA-Mediated Neurological Disorders

Towards Understanding RNA-Mediated Neurological Disorders. Ranhui Duan, Sumeet Sharma, Qiuping Xia, Kathryn Garber, Peng Jin; Journal of Genetics and Genomics, Available online 23 August 2014, ISSN 1673-8527, http://dx.doi.org/10.1016/j.jgg.2014.08.003.

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R loops are enriched over FXN intron 1 in cells with Friedreich ataxia-associated repeat expansions, compared to control cells. The formation of R loops precedes the presence of heterochromatin marks but correlates with epigenetic silencing of FXN and FMR1 and may be involved in the recruitment of enzymes involved in heterochromatinization.