Targeting Molecular Mediators of Ferroptosis and Oxidative Stress for Neurological Disorders

Abstract

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.

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

“…The infiltration and activation of immune cells in the acute period following TBI leads to the generation of ROS and RNS, further worsening oxidative stress [ 8 ]. Excitotoxicity and oxidative stress are also linked, as excessive excitatory stimulation and mitochondrial stress in the acute phase of TBI leads to the generation of ROS [ 80 ]. Furthermore, the NMDA and AMPA receptors involved in propagation of excitotoxicity are linked through the protein PSD95, which not only acts to amplify excitation early in the acute phase of TBI but also activates neuronal nitric oxide synthase, increasing the generation of RNS, with this relationship most apparent 24–48 h after TBI [ 69 ].…”

Oxidative Stress in Age-Related Neurodegenerative Diseases: An Overview of Recent Tools and Findings

“…Numerous molecular mediators of ferroptosis have been suggested as pharmaceutical targets, including nuclear factor erythroid 2-related factor-antioxidant response element (Nrf2-ARE), n-acetylcysteine (NAC), Fe 2+ , NADPH, and its oxidases NOX, among others [40], underlying its significance in pathological conditions.…”

The “Irony” of Ferroptosis: A Review on Neurological Challenges

“…Tf-Tfr complex triggers for the next cell cycle. During neurological disorders, excessive iron produces a large volume of ROS, which cause ferroptosis [5].…”