The calcium–iron connection in ferroptosis-mediated neuronal death
Free Radical Biology and Medicine(2021)
Abstract
Iron, through its participation in oxidation/reduction processes, is essential for the physiological function of biological systems. In the brain, iron is involved in the development of normal cognitive functions, and its lack during development causes irreversible cognitive damage. Yet, deregulation of iron homeostasis provokes neuronal damage and death. Ferroptosis, a newly described iron-dependent cell death pathway, differs at the morphological, biochemical, and genetic levels from other cell death types. Ferroptosis is characterized by iron-mediated lipid peroxidation, depletion of the endogenous antioxidant glutathione and altered mitochondrial morphology. Although iron promotes the emergence of Ca2+ signals via activation of redox-sensitive Ca2+ channels, the role of Ca2+ signaling in ferroptosis has not been established. The early dysregulation of the cellular redox state observed in ferroptosis is likely to disturb Ca2+ homeostasis and signaling, facilitating ferroptotic neuronal death. This review presents an overview of the role of iron and ferroptosis in neuronal function, emphasizing the possible involvement of Ca2+ signaling in these processes. We propose, accordingly, that the iron-ferroptosis-Ca2+ association orchestrates the progression of cognitive dysfunctions and memory loss that occurs in neurodegenerative diseases. Therefore, to prevent iron dyshomeostasis and ferroptosis, we suggest the use of drugs that target the abnormal Ca2+ signaling caused by excessive iron levels as therapy for neurological disorders.
MoreTranslated text
Key words
Calcium,Iron,Ferroptosis,Reactive oxygen species,Oxidative stress,Calcium release channels,Neurodegeneration,Ferroptosis inhibitors
AI Read Science
Must-Reading Tree
Example
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined