Lei Peng, Walker Tara, Ayton Scott
Department of Neurology and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, St Lucia, Queensland, Australia.
Nat Rev Neurosci. 2025 May 19. doi: 10.1038/s41583-025-00930-5.
Ferroptosis is a type of cell death process defined by iron-dependent peroxidation of phospholipids leading to the destruction of cellular membranes and death of the cell. Ferroptosis occurs throughout the body, but a considerable research focus on ferroptosis in the brain - neuroferroptosis - has been driven by the rich lipid and iron content of the brain as well as its high oxygen consumption. Neurons also have an exceptionally large surface area and metabolic demand, which necessitates specific mechanisms (such as lipid antioxidants) to engage constantly to protect the plasma membrane against lipid peroxidation. Ferroptosis has been extensively linked to neurodegeneration and ischaemia and is increasingly implicated in physiological processes such as neuronal reprogramming. Astrocytes provide metabolic support to neurons, enabling them to defend against ferroptosis, yet ferroptotic signals in microglia can propagate damage to astrocytes and neurons, highlighting the complex intercellular (patho)physiology of neuroferroptosis.
铁死亡是一种细胞死亡过程,其定义为磷脂的铁依赖性过氧化作用导致细胞膜破坏和细胞死亡。铁死亡发生在全身,但由于大脑富含脂质和铁以及高耗氧量,大量研究聚焦于大脑中的铁死亡——神经铁死亡。神经元还具有异常大的表面积和代谢需求,这就需要特定机制(如脂质抗氧化剂)持续发挥作用,以保护质膜免受脂质过氧化的影响。铁死亡已被广泛认为与神经退行性变和缺血有关,并且越来越多地涉及神经元重编程等生理过程。星形胶质细胞为神经元提供代谢支持,使其能够抵御铁死亡,然而小胶质细胞中的铁死亡信号可将损伤传播至星形胶质细胞和神经元,这凸显了神经铁死亡复杂的细胞间(病理)生理学。
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