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Review
. 2019 Jul;56(7):4880-4893.
doi: 10.1007/s12035-018-1403-3. Epub 2018 Nov 8.

Ferroptosis and Its Role in Diverse Brain Diseases

Abigail Weiland  1 , Yamei Wang  2 , Weihua Wu  2 , Xi Lan  1 , Xiaoning Han  1 , Qian Li  3   4 , Jian Wang  5
Affiliations
Review

Ferroptosis and Its Role in Diverse Brain Diseases

Abigail Weiland et al. Mol Neurobiol. 2019 Jul.

Abstract

Ferroptosis is a recently identified, iron-regulated, non-apoptotic form of cell death. It is characterized by cellular accumulation of lipid reactive oxygen species that ultimately leads to oxidative stress and cell death. Although first identified in cancer cells, ferroptosis has been shown to have significant implications in several neurologic diseases, such as ischemic and hemorrhagic stroke, Alzheimer's disease, and Parkinson's disease. This review summarizes current research on ferroptosis, its underlying mechanisms, and its role in the progression of different neurologic diseases. Understanding the role of ferroptosis could provide valuable information regarding treatment and prevention of these devastating diseases.

Keywords: Brain disease; Cancer; Ferroptosis; Stroke.

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Conflict of interest statement

Conflict of interest statement: The authors have declared that no conflict of interest exists.

Figures

Figure 1.
Figure 1.. Induction and inhibition of ferroptosis.
Ferroptosis is induced by lethal lipid peroxidation in the central nervous system. Dysregulation of intracellular iron metabolism and/or glutathione peroxidation pathways leads to accumulation of lipid reactive oxygen species (ROS) and eventually causes cell death. Various inducers and inhibitors are shown. Arrows indicate promotion; blunt-ended lines indicate inhibition. ATF4, activating transcription factor 4; DFO, deferoxamine; FINO2, 1, 2-dioxolane; FINs, ferroptosis-inducing agents; FtMt, mitochondrial ferritin; GPX4, glutathione peroxidase 4; GSH, glutathione; HMOX1, heme oxygenase-1; HpETE, hydroperoxyeicosatetraenoic acid; KEAP1, Kelch-like ECH-associated protein 1; LOX, lipoxygenase; PE, phosphatidylethanolamine; PEBP1, phosphatidylethanolamine-binding protein 1; PUFA, polyunsaturated fatty acid; RSL3, Ras-selective lethal 3; TF, transferrin; TFR, transferrin receptor; VDAC2/3, voltage-dependent anion channel 2/3; WA, withaferin A.
Figure 2.
Figure 2.. The role of ferroptosis in diverse brain diseases.
Various inducers and inhibitors in different brain diseases are shown. AD, Alzheimer’s disease; CoQ10, coenzyme Q10; DFO, deferoxamine; DPI, diphenylene iodonium; Fer-1, ferrostatin-1; Flt3, FMS-like tyrosine kinase-3; PD, Parkinson’s disease; PI3Kα, phosphatidylinositol 3-kinase α; PVL, periventricular leukomalacia; RSL3, Ras-selective lethal 3; WA, withaferin A.
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