The brain has a very high oxygen consumption rate and is particularly sensitive to oxidative stress. It is also the last organ to suffer from a loss of selenium (Se) in case of deficiency. Se is a crucial trace element present in the form of selenocysteine, the 21st proteinogenic amino acid present in selenoproteins, an essential protein family in the brain that participates in redox signaling. Among the most abundant selenoproteins in the brain are glutathione peroxidase 4 (GPX4), which reduces lipid peroxides and prevents ferroptosis, and selenoproteins W, I, F, K, M, O and T. Remarkably, more than half of them are proteins present in the ER and recent studies have shown their involvement in the maintenance of ER homeostasis, glycoprotein folding and quality control, redox balance, ER stress response signaling pathways and Ca²⁺ homeostasis. However, their molecular functions remain mostly undetermined. The ER is a highly specialized organelle in neurons that maintains the physical continuity of axons over long distances through its continuous distribution from the cell body to the nerve terminals. Alteration of this continuity can lead to degeneration of distal axons and subsequent neuronal death. Elucidation of the function of ER-resident selenoproteins in neuronal pathophysiology may therefore become a new perspective for understanding the pathophysiology of neurological diseases. Here we summarize what is currently known about each of their molecular functions and their impact on the nervous system during development and stress.

大脑的耗氧率非常高，对氧化应激特别敏感。它也是硒 (Se) 缺乏时最后一个损失的器官。Se 是一种重要的微量元素，以硒代半胱氨酸的形式存在，硒代半胱氨酸是硒蛋白中的第 21 个蛋白氨基酸，硒蛋白是大脑中参与氧化还原信号传导的重要蛋白质家族。大脑中最丰富的硒蛋白包括谷胱甘肽过氧化物酶 4 (GPX4)，它可以减少脂质过氧化物并防止铁死亡，以及硒蛋白 W、I、F、K、M、O 和 T。值得注意的是，其中一半以上是蛋白质最近的研究表明它们参与 ER 稳态的维持、糖蛋白折叠和质量控制、氧化还原平衡、ER 应激反应信号通路和 Ca ²⁺稳态。然而，它们的分子功能大多仍未确定。ER 是神经元中高度专业化的细胞器，通过从细胞体到神经末梢的连续分布，维持轴突长距离的物理连续性。这种连续性的改变可能导致远端轴突退化和随后的神经元死亡。因此，阐明内质网驻留硒蛋白在神经病理生理学中的功能可能成为理解神经系统疾病病理生理学的新视角。在这里，我们总结了目前已知的它们的每种分子功能及其在发育和应激过程中对神经系统的影响。