山东第一医科大学魏义举等研究人员合作总结了，泛素-蛋白酶体系统介导的铁死亡在神经系统疾病中的作用与机制。这一论文于2025年1月7日在线发表在国际学术期刊《神经科学通报》上。

研究人员综述了泛素-蛋白酶体系统（UPS）如何调节铁代谢、铁死亡及其在神经系统疾病中的相互作用。此外，研究人员还讨论了小分子抑制剂的未来应用，并识别了潜在的药物靶点。进一步研究UPS介导的铁死亡机制将为神经系统疾病的治疗干预和临床应用提供新的见解和策略。

研究人员表示，铁死亡是一种由细胞内铁浓度失衡引发的细胞死亡形式，导致脂质过氧化增强。在神经系统疾病中，氧化应激和线粒体损伤均可促进铁死亡，进而引起神经细胞功能障碍和死亡。UPS是一个细胞途径，其中特定蛋白质通过泛素标记以供蛋白酶体识别和降解。在神经疾病中，UPS在调节铁代谢和铁死亡中发挥重要作用。

附：英文原文

Title: The Role and Mechanisms of Ubiquitin-Proteasome System-Mediated Ferroptosis in Neurological Disorders

Author: Liu, Xin, Wang, Wei, Nie, Qiucheng, Liu, Xinjing, Sun, Lili, Ma, Qiang, Zhang, Jie, Wei, Yiju

Issue&Volume: 2025-01-07

Abstract: Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations, leading to enhanced lipid peroxidation. In neurological disorders, both oxidative stress and mitochondrial damage can contribute to ferroptosis, resulting in nerve cell dysfunction and death. The ubiquitin-proteasome system (UPS) refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome. In neurological conditions, the UPS plays a significant role in regulating ferroptosis. In this review, we outline how the UPS regulates iron metabolism, ferroptosis, and their interplay in neurological diseases. In addition, we discuss the future application of small-molecule inhibitors and identify potential drug targets. Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applications in neurological diseases.

DOI: 10.1007/s12264-024-01343-7

Source: https://link.springer.com/article/10.1007/s12264-024-01343-7