Dysregulation of Iron Homeostasis in the Central Nervous System and the Role of Ferroptosis in Neurodegenerative Disorders

作者：Samuel David, Priya Jhelum, Fari Ryan, Suh Young Jeong, Antje Kroner · 发表于：Antioxidants and Redox Signaling · 年份：2021 · DOI：10.1089/ars.2021.0218 · 被引用次数：137 · 研究领域：Trace Elements in Health、Iron Metabolism and Disorders、Ferroptosis and cancer prognosis

Significance: Iron accumulation occurs in the central nervous system (CNS) in a variety of neurological conditions as diverse as spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, and others. Iron is a redox-active metal that gives rise to damaging free radicals if its intracellular levels are not controlled or if it is not properly sequestered within cells. The accumulation of iron occurs due to dysregulation of mechanisms that control cellular iron homeostasis. Recent Advances: The molecular mechanisms that regulate cellular iron homeostasis have been revealed in much detail in the past three decades, and new advances continue to be made. Understanding which aspects of iron homeostasis are dysregulated in different conditions will provide insights into the causes of iron accumulation and iron-mediated tissue damage. Recent advances in iron-dependent lipid peroxidation leading to cell death, called ferroptosis, has provided useful insights that are highly relevant for the lipid-rich environment of the CNS. Critical Issues: This review examines the mechanisms that control normal cellular iron homeostasis, the dysregulation of these mechanisms in neurological disorders, and more recent work on how iron can induce tissue damage via ferroptosis. Future Directions: Quick and reliable tests are needed to determine if and when ferroptosis contributes to the pathogenesis of neurological disorders. In addition, there is need to develop better druggable agents to sca...