Impact of Oxidative Stress-Driven Ferroptosis in Neurodegeneration.
Impact of Oxidative Stress-Driven Ferroptosis in Neurodegeneration.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Guelph, CA · Author affiliation
Human Health Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.Location evidence
A plain-language reading has not been prepared for this paper yet.
Original abstract
Ferroptosis is an iron-dependent cell death driven by lipid peroxidation and failure of cellular antioxidant defenses. It is triggered by oxidative stress and can be aggravated by aging, inflammation, and dysregulation of iron homeostasis. In the central nervous system, iron dyshomeostasis, mitochondrial dysfunction, and membrane lipid remodeling can amplify oxidative injury and increase susceptibility to ferroptotic damage, particularly in vulnerable neurons. There is growing evidence that ferroptosis-related processes are linked to Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. This review addresses novel approaches to track ferroptosis in vivo, such as imaging and biomarker techniques, and important molecular mechanisms linking iron metabolism, reactive oxygen species, and PUFA-driven lipid peroxidation to neuronal damage. We also explore upstream transcriptional control via NRF2, iron chelation and iron-handling modulation, inhibition of lipid peroxidation, and reinforcement of the System Xc-GSH-GPX4 and CoQ10-linked defense pathways. Subsequently, we highlight translational issues that need attention to further progress ferroptosis-targeted therapies for neurodegenerative disease.