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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 487534, 10 pages
Review Article

Neurodegeneration in Friedreich’s Ataxia: From Defective Frataxin to Oxidative Stress

1Instituto Tecnologia Química e Biológica, Universidade Nova de Lisboa, Avenida da República, 2784-505 Oeiras, Portugal
2Development of the Nervous System, IBENS, Ecole Normale Supérieure, 46 rue d’Ulm, 75230 Paris Cedex 05, France

Received 26 May 2013; Accepted 14 June 2013

Academic Editor: Anne-Laure Bulteau

Copyright © 2013 Cláudio M. Gomes and Renata Santos. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Friedreich’s ataxia is the most common inherited autosomal recessive ataxia and is characterized by progressive degeneration of the peripheral and central nervous systems and cardiomyopathy. This disease is caused by the silencing of the FXN gene and reduced levels of the encoded protein, frataxin. Frataxin is a mitochondrial protein that functions primarily in iron-sulfur cluster synthesis. This small protein with an α/β sandwich fold undergoes complex processing and imports into the mitochondria, generating isoforms with distinct N-terminal lengths which may underlie different functionalities, also in respect to oligomerization. Missense mutations in the FXN coding region, which compromise protein folding, stability, and function, are found in 4% of FRDA heterozygous patients and are useful to understand how loss of functional frataxin impacts on FRDA physiopathology. In cells, frataxin deficiency leads to pleiotropic phenotypes, including deregulation of iron homeostasis and increased oxidative stress. Increasing amount of data suggest that oxidative stress contributes to neurodegeneration in Friedreich’s ataxia.