An Overview of the Ferroptosis Hallmarks in Friedreich's Ataxia.

BACKGROUND: Friedreich's ataxia (FRDA) is a neurodegenerative disease characterized by early mortality due to hypertrophic cardiomyopathy. FRDA is caused by reduced levels of frataxin (FXN), a mitochondrial protein involved in the synthesis of iron-sulphur clusters, leading to iron accumulation at the mitochondrial level, uncontrolled production of reactive oxygen species and lipid peroxidation. These features are also common to ferroptosis, an iron-mediated type of cell death triggered by accumulation of lipoperoxides with distinct morphological and molecular characteristics with respect to other known cell deaths.

SCOPE OF REVIEW: Even though ferroptosis has been associated with various neurodegenerative diseases including FRDA, the mechanisms leading to disease onset/progression have not been demonstrated yet. We describe the molecular alterations occurring in FRDA that overlap with those characterizing ferroptosis.

MAJOR CONCLUSIONS: The study of ferroptotic pathways is necessary for the understanding of FRDA pathogenesis, and anti-ferroptotic drugs could be envisaged as therapeutic strategies to cure FRDA.