Iron in Friedreich Ataxia: A Central Role in the Pathophysiology or an Epiphenomenon?
David AlsinaRosa PurroyJoaquim RosJordi TamaritPublished in: Pharmaceuticals (Basel, Switzerland) (2018)
Friedreich ataxia is a neurodegenerative disease with an autosomal recessive inheritance. In most patients, the disease is caused by the presence of trinucleotide GAA expansions in the first intron of the frataxin gene. These expansions cause the decreased expression of this mitochondrial protein. Many evidences indicate that frataxin deficiency causes the deregulation of cellular iron homeostasis. In this review, we will discuss several hypotheses proposed for frataxin function, their caveats, and how they could provide an explanation for the deregulation of iron homeostasis found in frataxin-deficient cells. We will also focus on the potential mechanisms causing cellular dysfunction in Friedreich Ataxia and on the potential use of the iron chelator deferiprone as a therapeutic agent for this disease.
Keyphrases
- end stage renal disease
- early onset
- iron deficiency
- oxidative stress
- chronic kidney disease
- newly diagnosed
- ejection fraction
- poor prognosis
- induced apoptosis
- genome wide
- gene expression
- prognostic factors
- copy number
- healthcare
- mitochondrial dna
- small molecule
- dna methylation
- cell cycle arrest
- long non coding rna
- transcription factor
- patient reported
- duchenne muscular dystrophy