Hepcidin, an emerging and important player in brain iron homeostasis

Driton Vela. Journal of Translational Medicine 201816:25 doi:10.1186/s12967-018-1399-5

Iron dysregulation has been observed consistently in different organs in Friedreich ataxia (FA). This disease affects CNS by causing neurodegenerative damages in dentate nuclei of the cerebellum, dorsal root ganglia, but also in cerebrum, thalamus and other structures. FA is caused by a defective frataxin, which main functions include involvement in iron-sulfur cluster formation and in iron delivery to ferrochelatase. Although some observations did find iron accumulation in dentate nuclei in FA patients, other studies have revealed a pattern of iron redistribution, rather than iron accumulation in FA. Studies suggest that iron dysregulation in FA is not needed for neurodegeneration to occur, while animal models reveal tissue-specific damages due to frataxin deficiency. These differences are related with levels of frataxin expression, where most of the damage is observed in tissues with higher expression of frataxin, such as the heart and dorsal root ganglia. In the heart, inflammatory infiltrate produces hepcidin and has been proposed as one of the pathogenic mechanisms of heart damage in FA. Frataxin deficiency in animal models can cause a strong inflammatory reaction in Schwann cells, which are known to enwrap neurons of dorsal root ganglia. These neurons are frequently affected in FA and are characterized with iron dysregulation and inappropriate myelination. But, hepcidin expression in these cells has not been studied in models of FA, therefore it is not known what role, if any, does hepcidin have in the pathophysiology of neurodegeneration in FA.

Hepcidin, an emerging and important player in brain iron homeostasis