**1. Introduction**

The current classification system of cell death has been updated by the Nomenclature Committee on Cell Death (NCCD), according to their guidelines for the definition and interpretation of all aspects of cell death [1,2]. Accidental cell death (ACD) is an instantaneous and catastrophic demise of cells exposed to severe insults of physical or mechanical forces. On the other hand, regulated cell death (RCD) is a dedicated molecular machinery [3]. RCD can occur in two ways: firstly, as programmed cell death that can occur in the absence of any exogenous environmental perturbation. Secondly, RCD can originate from disturbances of the intracellular or extracellular microenvironment that cannot be restored to cellular homeostasis [4–6].

In 2012, Brent R. Stockwell described a unique form of cell death that results from the overwhelming iron-dependent accumulation of lethal amounts of lipid-based reactive oxygen species and named it ferroptosis [7]. Ferroptosis is morphologically and biochemically distinct from other RCDs. It occurs without the chromatin condensation and nuclear reduction seen in apoptosis, cellular and organellar swelling of necrosis, and without the common features of autophagy. Morphologically, only mitochondrial shrinkage distinguishes it from other forms of death [8,9]. Ferroptotic cell death is associated with the iron-dependent mechanism and formation of extremely reactive free radicals, along with severe peroxidation of membrane phospholipids (PLs) rich in polyunsaturated fatty acids (PUFAs), mainly of arachidonic or adrenic acids from phosphatidyl ethanolamine (PE) molecules [10–12].

The complex balance between reactive oxygen species (ROS) and the antioxidant system maintains cell homeostasis by removing dangerous stimuli and controlling oxidative stress by several factors, and is also present in the central nervous system (CNS) [13,14]. Among these factors, system xc−, an amino acid antiporter, maintains the synthesis of glutathione (GSH) and oxidative protection. Inhibition of system xc− causes a rapid drop of intracellular glutathione levels and cell death caused by the accumulation of lipid-derived ROS. Lipid and protein oxidation lead to inflammation and changes in DNA, and are the trigger for premature aging, loss of function and death of neurons. The increase in oxidative stress generated by free radicals associated with uncontrolled intracellular iron metabolism has been associated with the pathophysiology of neurodegenerative diseases [13–15]. Here we address the main pathways of ferroptosis and its role in the pathophysiology of Alzheimer's disease, Parkinson's disease, and Huntington's disease, the main neurodegenerative diseases in which ferroptosis has been shown to be involved.
