Table 2.

Key Mechanisms and Regulators of Ferroptosis in Nervous System Diseases

Diseases		Key Mechanisms	Regulators	References
AD		Iron overload Decrease FPN expression Decrease SLC7A11, GSH, and GPX4 protein levels Increase NCOA4 protein levels	Inhibitor: γ-glutamylcysteine Deferoxamine LA	[119,123,128–131,133]
PD		Iron overload Ferritinophagy and increased DMT1 expression Decrease SLC7A11 and GSH protein levels Decrease CoQ10 protein levels	Inhibitor: Deferiprone Clioquinol	[136,137,139,141–143]
HD		Iron overload Decrease GSH protein level	Inhibitor: Fer-1	[18,148,150]
Epilepsy		Iron overload Increase extracellular glutamate level Decrease GSH and GPX4 protein levels	Inhibitor: Fer-1 EPI-743	[153–155]
Gliomas		Increase intracellular glutamate level Decrease ACSL4 expression Increase GPX4 and FSP1 expression	Inducer: PAB IONPs	[37,158,159,161,162]
Strokes	Ischemic Strokes	Iron overload Decrease SLC7A11, GSH and GPX4 protein levels Decrease CoQ10 protein levels	Inhibitor: Fer-1 Lip-1	[19,168,170,172]
	Hemorrhagic Strokes	Iron overload Increase ROS level	Inhibitor: Fer-1 PIH N-acetylcysteine PGE2	[174,176,178–180]
TBI		Iron and ROS accumulation Decrease GPX4 activity Increase COX2, 15-LOX and ACSL4 protein levels	Inhibitor: Fer-1 Melatonin Polydatin	[20,183–185]

Abbreviations: AD, Alzheimer’s disease; FPN, ferroportin; GSH, glutathione; GPX4, glutathione peroxidase 4; NCOA4, nuclear receptor coactivator 4; LA, alpha-lipoic acid; PD, Parkinson’s disease; CoQ10, coenzyme Q10; HD, Huntington’s disease; Fer-1, ferrostatin-1; EPI-743, vatiquinone; Lip-1, liproxstatin-1; ROS, reactive oxygen species; PIH, pyridoxal isonicotinoyl hydrazine; PGE2, prostaglandin E2; 12/15-LOX, 12/15-lipoxygenase; ACSL4, acyl-CoA synthetase long-chain family member 4; FSP1, ferroptosis suppressor protein 1; PAB, pseudolaric acid B; IONPs, iron oxide nanoparticles; TBI, traumatic brain injury; COX2, cytochrome c oxidase subunit 2.