Journal article
lBeyond Loss of Frataxin: the Complex Molecular Pathology of Friedreich Ataxia
MArguerite V Evans-Galea, Paul J Lockhart, Charles A Galea, Anthony J Hannan, Martin B Delatycki
DISCOVERY MEDICINE | DISCOVERY MEDICINE | Published : 2014
Abstract
Friedreich ataxia (FRDA) is a devastating neurodegenerative disease caused by mutations in the frataxin gene (FXN). Frataxin is an essential protein which localizes to the mitochondria and is required for the synthesis of iron-sulfur clusters and heme. Most individuals with FRDA are homozygous for trinucleotide GAA.TTC repeat expansions in intron 1 of FXN. The instability of these GAA.TTC repeats, the formation of non-B DNA GAA.TTC structures, and accompanying epigenetic changes lead to reduced FXN transcript and frataxin protein. This 'loss of frataxin' is considered the main driver of disease pathology with mitochondria-rich tissues such as the heart and the brain most affected. While our ..
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Funding Acknowledgements
The authors are funded by the National Health and Medical Council of Australia (Project Grants to M.B.D., P.J.L., & M.V.E-G; Practitioner Fellowship to M.B.D; Career Development Fellowship to P.J.L.); the Australian Research Council (FT3 Future Fellowship to A.J.H.); and the Victorian Government Operational Infrastructure Support Program.