Please use this identifier to cite or link to this item:
http://bura.brunel.ac.uk/handle/2438/8709
Title: | Interferon gamma upregulates frataxin and corrects the functional deficits in a Friedreich ataxia model |
Authors: | Tomassini, B Arcuri, G Fortuni, S Sandi, C Ezzatizadeh, V Casali, C Condò, I Malisan, F Al-Mahdawi, S Pook, M Testi, R |
Keywords: | Friedreich ataxia;Interferon-gamma;Frataxin;Animal model |
Issue Date: | 2012 |
Publisher: | Oxford University Press |
Citation: | Human Molecular Genetics, 21(13), 2855 - 2861, 2012 |
Abstract: | Friedreich's ataxia (FRDA) is the most common hereditary ataxia, affecting ∼3 in 100 000 individuals in Caucasian populations. It is caused by intronic GAA repeat expansions that hinder the expression of the FXN gene, resulting in defective levels of the mitochondrial protein frataxin. Sensory neurons in dorsal root ganglia (DRG) are particularly damaged by frataxin deficiency. There is no specific therapy for FRDA. Here, we show that frataxin levels can be upregulated by interferon gamma (IFNγ) in a variety of cell types, including primary cells derived from FRDA patients. IFNγ appears to act largely through a transcriptional mechanism on the FXN gene. Importantly, in vivo treatment with IFNγ increases frataxin expression in DRG neurons, prevents their pathological changes and ameliorates the sensorimotor performance in FRDA mice. These results disclose new roles for IFNγ in cellular metabolism and have direct implications for the treatment of FRDA. |
Description: | Copyright © The Author 2012. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
URI: | http://hmg.oxfordjournals.org/content/21/13/2855 http://bura.brunel.ac.uk/handle/2438/8709 |
DOI: | http://dx.doi.org/10.1093/hmg/dds110 |
ISSN: | 1460-2083 |
Appears in Collections: | Biological Sciences Dept of Life Sciences Research Papers |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Fulltext.pdf | 318.45 kB | Adobe PDF | View/Open |
Items in BURA are protected by copyright, with all rights reserved, unless otherwise indicated.