Liu Xin, Wang Wei, Nie Qiucheng, Liu Xinjing, Sun Lili, Ma Qiang, Zhang Jie, Wei Yiju
Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, China.
Biomedical Sciences College & Shandong Medicinal Biotechnology Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, China.
Neurosci Bull. 2025 Apr;41(4):691-706. doi: 10.1007/s12264-024-01343-7. Epub 2025 Jan 7.
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.
铁死亡是一种由细胞内铁浓度失衡引发的细胞死亡形式，会导致脂质过氧化增强。在神经疾病中，氧化应激和线粒体损伤均可促成铁死亡，从而导致神经细胞功能障碍和死亡。泛素-蛋白酶体系统（UPS）是一种细胞途径，特定蛋白质在此途径中被泛素标记，以便被蛋白酶体识别和降解。在神经疾病中，UPS在调节铁死亡方面发挥着重要作用。在本综述中，我们概述了UPS如何调节铁代谢、铁死亡及其在神经疾病中的相互作用。此外，我们讨论了小分子抑制剂的未来应用，并确定了潜在的药物靶点。对UPS介导的铁死亡机制的进一步研究将为神经疾病的治疗干预和临床应用提供新的见解和策略。
