As an iron-dependent regulated form of cell death, ferroptosis is characterized by iron-dependent lipid peroxidation and has been implicated in the occurrence and development of various diseases, including nervous system diseases and injuries. Ferroptosis has become a potential target for intervention in these diseases or injuries in relevant preclinical models. As a member of the Acyl-CoA synthetase long-chain family (ACSLs) that can convert saturated and unsaturated fatty acids, Acyl—CoA synthetase long-chain familymember4 (ACSL4) is involved in the regulation of arachidonic acid and eicosapentaenoic acid, thus leading to ferroptosis. The underlying molecular mechanisms of ACSL4-mediated ferroptosis will promote additional treatment strategies for these diseases or injury conditions. Our review article provides a current view of ACSL4-mediated ferroptosis, mainly including the structure and function of ACSL4, as well as the role of ACSL4 in ferroptosis. We also summarize the latest research progress of ACSL4-mediated ferroptosis in central nervous system injuries and diseases, further proving that ACSL4-medicated ferroptosis is an important target for intervention in these diseases or injuries.

Increasing evidence indicates a possible causal link between neuroinflammation and neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and stroke. A putative mechanism underlying such a link can be explained by ferroptosis. Current studies have shown that disturbances of iron homeostasis, glutamate excitatory toxicity, lipid reactive oxygen species (ROS), and other manifestations related to ferroptosis can be detected in several neurological disorders caused by neuroinflammation. To date, compelling evidence indicates that damage‐associated molecular pattern (DAMP) molecules (e.g., ROS) produced in the process of ferroptosis activate glial cells by activating neuroimmune pathways and then produce a series of inflammatory factors which contribute to neurological disorders. Our review article provides a current view of the involvement of ferroptosis or ROS in the pathological process of neuroinflammation, the effects of neuroinflammation mediated by ferroptosis in neurological disorders, a better understanding of the mechanisms underlying ferroptosis participates in neuroinflammation, and the potential treatments for neurological disorders. In addition, further research on the mechanisms of ferroptosis as well as the link between ferroptosis and neuroinflammation will help provide new targets for treatment.

With the acceleration of population aging, nervous system diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), anxiety, depression, stroke, and traumatic brain injury (TBI) have become a huge burden on families and society. The mechanism of neurological disorders is complex, which also lacks effective treatment, so relevant research is required to solve these problems urgently. Given that oxidative stress‐induced lipid peroxidation eventually leads to ferroptosis, both oxidative stress and ferroptosis are important mechanisms causing neurological disorders, targeting mediators of oxidative stress and ferroptosis have become a hot research direction at present. Our review provides a current view of the mechanisms underlying ferroptosis and oxidative stress participate in neurological disorders, the potential application of molecular mediators targeting ferroptosis and oxidative stress in neurological disorders. The target of molecular mediators or agents of oxidative stress and ferroptosis associated with neurological disorders, such as reactive oxygen species (ROS), nuclear factor erythroid 2–related factor‐antioxidant response element (Nrf2‐ARE), n‐acetylcysteine (NAC), Fe²⁺, NADPH, and its oxidases NOX, has been described in this article. Given that oxidative stress‐induced ferroptosis plays a pivotal role in neurological disorders, further research on the mechanisms of ferroptosis caused by oxidative stress will help provide new targets for the treatment of neurological disorders.