Dong Yimin, Zheng Meng, Ding Weizhong, Guan Hanfeng, Xiao Jun, Li Feng
Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Redox Biol. 2025 Apr;81:103551. doi: 10.1016/j.redox.2025.103551. Epub 2025 Feb 14.
Iron overload and related oxidative damage are seen in many rare diseases, due to mutation of iron homeostasis-related genes. As a core regulator on cellular antioxidant reaction, Nrf2 can also decrease systemic and cellular iron levels by regulating iron-related genes and pathways, making Nrf2 activators very good candidates for the treatment of iron overload disorders. Successful examples include the clinical use of omaveloxolone for Friedreich's Ataxia and dimethyl fumarate for relapsing-remitting multiple sclerosis. Despite these uses, the therapeutic potentials of Nrf2 activators for iron overload disorders may be overlooked in clinical practice. Therefore, this study talks about the potential use, possible mechanisms, and precautions of Nrf2 activators in treating rare iron overload diseases. In addition, a combination therapy with Nrf2 activators and iron chelators is proposed for clinical reference, aiming to facilitate the clinical use of Nrf2 activators for more iron overload disorders.
由于铁稳态相关基因的突变，铁过载及相关氧化损伤在许多罕见病中都有出现。作为细胞抗氧化反应的核心调节因子，Nrf2还可通过调节铁相关基因和通路来降低全身和细胞内的铁水平，这使得Nrf2激活剂成为治疗铁过载疾病的理想选择。成功案例包括奥伐莫酮用于治疗弗里德赖希共济失调以及富马酸二甲酯用于治疗复发缓解型多发性硬化症。尽管有这些应用，但在临床实践中，Nrf2激活剂治疗铁过载疾病的治疗潜力可能被忽视。因此，本研究探讨了Nrf2激活剂在治疗罕见铁过载疾病中的潜在用途、可能机制及注意事项。此外，还提出了Nrf2激活剂与铁螯合剂的联合疗法以供临床参考，旨在促进Nrf2激活剂在更多铁过载疾病中的临床应用。
