Iron Pathophysiology in Friedreich’s Ataxia

Li K. (2019) Iron Pathophysiology in Friedreich’s Ataxia. In: Chang YZ. (eds) Brain Iron Metabolism and CNS Diseases. Advances in Experimental Medicine and Biology, vol 1173. Springer, Singapore. DOI:10.1007/978-981-13-9589-5_7. Online ISBN: 978-981-13-9589-5

FXN is essential for mitochondrial function by the involvement of iron–sulfur cluster biogenesis. The effects of its deficiency also include disruption of cellular, particularly mitochondrial, iron homeostasis, i.e., relatively more iron accumulated in mitochondria and less iron presented in cytosol. Though iron toxicity is commonly thought to be mediated via Fenton reaction, oxidative stress seems not to be the main problem to result in detrimental effects on cell survival, particularly neuron survival. Therefore, the basic research on FXN function is urgently demanded to understand the disease. This chapter focuses on the outcome of FXN expression, regulation, and function in cellular or animal models of FRDA and on iron pathophysiology in the affected tissues. Finally, therapeutic strategies based on the control of iron toxicity and iron cellular redistribution are considered. The combination of multiple therapeutic targets including iron, oxidative stress, mitochondrial function, and FXN regulation is also proposed.