Centre for Research in Neuroscience, The Research Institute of the McGill University Health Centre, Montreal, Canada.
Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, Oregon, USA.
Antioxid Redox Signal. 2022 Jul;37(1-3):150-170. doi: 10.1089/ars.2021.0218. Epub 2022 Jan 4.
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. 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. 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 ferroptosis. 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 scavenge lipid radicals and reduce CNS damage for neurological conditions for which there are currently few effective treatments. 37, 150-170.
铁在中枢神经系统（CNS）中的积累发生在各种神经状况中，如脊髓损伤、中风、多发性硬化症、帕金森病等。铁是一种氧化还原活性金属，如果细胞内水平不受控制，或者不能在细胞内正确隔离，就会产生有害的自由基。铁的积累是由于控制细胞铁稳态的机制失调引起的。在过去的三十年中，调节细胞铁稳态的分子机制已经被详细揭示，新的进展仍在不断取得。了解不同条件下铁稳态的哪些方面失调，将为铁积累和铁介导的组织损伤的原因提供深入了解。最近在铁依赖性脂质过氧化导致细胞死亡（称为铁凋亡）方面的进展提供了非常相关的见解，这对富含脂质的 CNS 环境具有重要意义。这篇综述检查了控制正常细胞铁稳态的机制、这些机制在神经紊乱中的失调，以及铁如何诱导组织损伤和铁凋亡的最新进展。需要快速可靠的测试来确定铁凋亡是否以及何时有助于神经紊乱的发病机制。此外，还需要开发更好的可药物化的药物来清除脂质自由基，减少目前治疗效果不佳的神经状况下的中枢神经系统损伤。37, 150-170。
