Friedreich's ataxia: from disease mechanisms to therapeutic interventions.
Friedreich's ataxia (FRDA) is the most common inherited ataxia. FRDA is an autosomal recessive degenerative disorder caused by a GAA triplet expansion or point mutations in the FRDA gene on chromosome 9q13. The FRDA gene product, frataxin, is a widely expressed mitochondrial protein that is severely reduced in FRDApatients. The function of frataxin has not been established yet. Studies of the yeast and animal model of the disease as well as of tissues from FRDA patients have demonstrated that deficit of frataxin is associated with mitochondrial iron accumulation, increased sensitivity to oxidative stress, deficit of respiratory chain complex activities and in vivo impairment of tissue energy metabolism. Pilot studies have shown the potential effect of antioxidant therapy in this condition and provide a strong rationale for designing larger clinical randomized trials.
Lodi
Raffaele
R
Dipartimento di Medicina Clinica e Biotecnologia Applicata, Universita' di Bologna, Bologna, Italy. raffaele.lodi@unibo.it
Tonon
Caterina
C
Calabrese
Vittorio
V
Schapira
Anthony H V
AH