Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

• Published in: International journal of molecular sciences Vol. 21; no. 22; p. 8765
• Main Authors: Reichert, Cadiele Oliana, de Freitas, Fábio Alessandro, Sampaio-Silva, Juliana, Rokita-Rosa, Leonardo, Barros, Priscila de Lima, Levy, Debora, Bydlowski, Sérgio Paulo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.11.2020; MDPI
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amino acids; Apoptosis; Arachidonate 15-Lipoxygenase - genetics; Arachidonate 15-Lipoxygenase - metabolism; Arachidonic Acid - metabolism; Brain - metabolism; Brain - pathology; Cell Membrane - metabolism; Cell Membrane - pathology; Disease; Enzymes; Fatty acids; Fatty Acids, Unsaturated - metabolism; Ferroptosis; Free radicals; Glutathione; Glutathione - metabolism; Homeostasis; Humans; Huntington Disease - genetics; Huntington Disease - metabolism; Huntington Disease - pathology; Iron - metabolism; Lipid Peroxidation; Lipids; Membranes; Neurons - metabolism; Neurons - pathology; Oxidation; Oxidative Stress; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Pathophysiology; Phospholipid Hydroperoxide Glutathione Peroxidase - deficiency; Phospholipid Hydroperoxide Glutathione Peroxidase - genetics; Proteins; Review; iron metabolism; system xc; glutathione peroxidase 4; neurodegenerative diseases; ferroptosis; Alzheimer’s disease; cell death; Huntington’s disease; GSH; Parkinson’s disease
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21228765

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.