RÉSUMÉ
Ferroptosis is a type of cell death that was described less than a decade ago. It is caused by the excess of free intracellular iron that leads to lipid (hydro) peroxidation. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. Since the 1960s, increased concentration of iron in the central nervous system has been associated with oxidative stress, oxidation of proteins and lipids, and cell death. Here, we review the main mechanisms involved in the process of ferroptosis such as lipid peroxidation, glutathione peroxidase 4 enzyme activity, and iron metabolism. Moreover, the association of ferroptosis with the pathophysiology of some neurodegenerative diseases, namely Alzheimer's, Parkinson's, and Huntington's diseases, has also been addressed.
Sujet(s)
Maladie d'Alzheimer/métabolisme , Ferroptose , Maladie de Huntington/métabolisme , Fer/métabolisme , Neurones/métabolisme , Maladie de Parkinson/métabolisme , Phospholipid hydroperoxide glutathione peroxidase/génétique , Maladie d'Alzheimer/génétique , Maladie d'Alzheimer/anatomopathologie , Arachidonate 15-lipoxygenase/génétique , Arachidonate 15-lipoxygenase/métabolisme , Acide arachidonique/métabolisme , Encéphale/métabolisme , Encéphale/anatomopathologie , Membrane cellulaire/métabolisme , Membrane cellulaire/anatomopathologie , Acides gras insaturés/métabolisme , Glutathion/métabolisme , Humains , Maladie de Huntington/génétique , Maladie de Huntington/anatomopathologie , Peroxydation lipidique , Neurones/anatomopathologie , Stress oxydatif , Maladie de Parkinson/génétique , Maladie de Parkinson/anatomopathologie , Phospholipid hydroperoxide glutathione peroxidase/déficitRÉSUMÉ
Cardiac autonomic neuropathy is a neglected diabetic chronic complication for which genetic predictors are rarely reported. Oxidative stress is implicated in the pathogenesis of microvascular complications, and glutathione peroxidase 4 is involved in the detoxification of peroxides and of reactive oxygen species. Thus, the association of a functional variant in the gene encoding glutathione peroxidase 4 (rs713041) with this diabetic complication was investigated in 341 individuals with type 1 diabetes evaluated for cardiac autonomic neuropathy status (61.7% women, 34 [27-42] years old; diabetes duration: 21 [15-27] years; HbA1c: 8.3% [7.4-9.4]; as median [interquartile interval]). Cardiac autonomic neuropathy was present in 29% of the participants. There was an inverse association of the minor T allele of rs713041 with cardiac autonomic neuropathy (odds ratio = 0.39; 95% confidence interval = 0.17-0.90; p = 0.0271) after adjustment for potential confounders. The functional glutathione peroxidase 4 variant rs713041 modulated the risk for cardiac autonomic neuropathy in the studied population with type 1 diabetes.