程序性细胞死亡
细胞生物学
脂质过氧化
平衡
细胞凋亡
信号转导
氧化应激
GPX4
神经科学
化学
线粒体
生物
生物化学
超氧化物歧化酶
谷胱甘肽过氧化物酶
作者
Silvia Gleitze,Andrea Paula-Lima,Marco T. Núñez,Cecilia Hidalgo
标识
DOI:10.1016/j.freeradbiomed.2021.08.231
摘要
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.
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