Document Detail


Friedreich's ataxia: Past, present and future.
MedLine Citation:
PMID:  21550666     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterized by progressive gait and limb ataxia, dysarthria, areflexia, loss of vibratory and position sense, and a progressive motor weakness of central origin. Additional features include hypertrophic cardiomyopathy and diabetes. Large GAA repeat expansions in the first intron of the FXN gene are the most common mutation underlying FRDA. Patients show severely reduced levels of a FXN-encoded mitochondrial protein called frataxin. Frataxin deficiency is associated with abnormalities of iron metabolism: decreased iron-sulfur cluster (ISC) biogenesis, accumulation of iron in mitochondria and depletion in the cytosol, enhanced cellular iron uptake. Some models have also shown reduced heme synthesis. Evidence for oxidative stress has been reported. Respiratory chain dysfunction aggravates oxidative stress by increasing leakage of electrons and the formation of superoxide. In vitro studies have demonstrated that Frataxin deficient cells not only generate more free radicals, but also show a reduced capacity to mobilize antioxidant defenses. The search for experimental drugs increasing the amount of frataxin is a very active and timely area of investigation. In cellular and in animal model systems, the replacement of frataxin function seems to alleviate the symptoms or even completely reverse the phenotype. Therefore, drugs increasing the amount of frataxin are attractive candidates for novel therapies. This review will discuss recent findings on FRDA pathogenesis, frataxin function, new treatments, as well as recent animal and cellular models. Controversial aspects are also discussed.
Authors:
Daniele Marmolino
Related Documents :
16608326 - Organocatalytic direct michael reaction of ketones and aldehydes with beta-nitrostyrene...
15816756 - Direct amino acid-catalyzed asymmetric desymmetrization of meso-compounds: tandem amino...
15479086 - P-menthane-3-carboxaldehyde: a useful chiral auxiliary for the synthesis of chiral quat...
16323846 - Diastereoselective intramolecular alpha-amidoalkylation reactions of l-dopa derivatives...
10908866 - Optimization of the production of aroma compounds by kluyveromyces marxianus in solid-s...
24090186 - Synthesis of alpha-aminonitriles with benzimidazolic and theophyllinic backbones using ...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-17
Journal Detail:
Title:  Brain research reviews     Volume:  -     ISSN:  1872-6321     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-5-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101300366     Medline TA:  Brain Res Rev     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Newborn preference for a new face vs. a previously seen communicative or motionless face.
Next Document:  CHRNA7 haplotypes are associated with impaired attention in euthymic bipolar disorder.