Ferroptosis Mechanisms Involved in Neurodegenerative Diseases.

Cadiele Oliana Reichert, Fábio Alessandro de Freitas, Juliana Sampaio-Silva, Leonardo Rokita-Rosa, Priscila de Lima Barros, Debora Levy, Sérgio Paulo Bydlowski

Journal: International journal of molecular sciences 2021;21(22):8765

PMID: 33233496

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Abstract

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.

Address: Lipids, Oxidation, and Cell Biology Group, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403-900, Brazil.; Instituto Nacional de Ciencia e Tecnologia em Medicina Regenerativa (INCT-Regenera), CNPq, Rio de Janeiro 21941-902, Brazil.

DOI: 10.3390/ijms21228765

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MeSH Terms: Alzheimer Disease, Arachidonate 15-Lipoxygenase, Arachidonic Acid, Brain, Cell Membrane, Fatty Acids, Unsaturated, Ferroptosis, Glutathione, Humans, Huntington Disease, Iron, Lipid Peroxidation, Neurons, Oxidative Stress, Parkinson Disease, Phospholipid Hydroperoxide Glutathione Peroxidase