Ferroptosis in Friedreich’s Ataxia: A Metal-Induced Neurodegenerative Disease

Biomolecules

MariaTeresa Fiorenza¹  PiergiorgioLa Rosa¹  EnricoSilvio Bertini²  Fiorella Piemonte²  Sara Petrillo² 

[1] Department of Psychology, Division of Neuroscience, Sapienza University of Rome, 00185 Rome, Italy;Unit of Muscular and Neurodegenerative Diseases, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy;

关键词: ferroptosis;    Friedreich’s Ataxia;    iron;    neurodegeneration;    oxidative stress;   

DOI  :  10.3390/biom10111551

来源: DOAJ

【 摘 要 】

Ferroptosis is an iron-dependent form of regulated cell death, arising from the accumulation of lipid-based reactive oxygen species when glutathione-dependent repair systems are compromised. Lipid peroxidation, mitochondrial impairment and iron dyshomeostasis are the hallmark of ferroptosis, which is emerging as a crucial player in neurodegeneration. This review provides an analysis of the most recent advances in ferroptosis, with a special focus on Friedreich’s Ataxia (FA), the most common autosomal recessive neurodegenerative disease, caused by reduced levels of frataxin, a mitochondrial protein involved in iron–sulfur cluster synthesis and antioxidant defenses. The hypothesis is that the iron-induced oxidative damage accumulates over time in FA, lowering the ferroptosis threshold and leading to neuronal cell death and, at last, to cardiac failure. The use of anti-ferroptosis drugs combined with treatments able to activate the antioxidant response will be of paramount importance in FA therapy, such as in many other neurodegenerative diseases triggered by oxidative stress.

【 授权许可】

Unknown