Xu Jingyi, Shen Rongjing, Qian Mengting, Zhou Zhengjun, Xie Bingqing, Jiang Yong, Yu Yang, Dong Wei
Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, 646000 Luzhou, Sichuan, China.
Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China.
J Integr Neurosci. 2025 Apr 24;24(4):25845. doi: 10.31083/JIN25845.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by the formation of amyloid plaques, neurofibrillary tangles and progressive cognitive decline. Amyloid-beta peptide (Aβ) monoclonal antibody therapeutic clinical trials have nearly failed, raising significant concerns about other etiological hypotheses about AD. Recent evidence suggests that AD patients also exhibit persistent neuronal loss and neuronal death accompanied by brain iron deposition or overload-related oxidative stress. Ferroptosis is a type of cell death that depends on iron, unlike autophagy and apoptosis. Inhibiting neuronal ferroptosis function is effective in improving cognitive impairment in AD. Notably, new research shows that ferroptosis in AD is crucially dependent on glial cell activation. This review examines the relationship between the imbalance of iron metabolism, the regulation of iron homeostasis in glial cells and neuronal death in AD pathology. Finally, the review summarizes some current drug research in AD targeting iron homeostasis, many novel iron-chelating compounds and natural compounds showing potential AD-modifying properties that may provide therapeutic targets for treating AD.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征为淀粉样斑块形成、神经原纤维缠结以及进行性认知衰退。β-淀粉样肽（Aβ）单克隆抗体治疗的临床试验几乎失败，这引发了人们对AD其他病因假说的重大担忧。最近的证据表明，AD患者还表现出持续性神经元丢失和神经元死亡，并伴有脑铁沉积或与铁过载相关的氧化应激。铁死亡是一种不同于自噬和凋亡的依赖于铁的细胞死亡类型。抑制神经元铁死亡功能可有效改善AD中的认知障碍。值得注意的是，新研究表明，AD中的铁死亡关键依赖于胶质细胞激活。本综述探讨了铁代谢失衡、胶质细胞中铁稳态调节与AD病理学中神经元死亡之间的关系。最后，该综述总结了目前一些针对AD中铁稳态的药物研究，许多新型铁螯合化合物和天然化合物显示出潜在的AD改善特性，可能为治疗AD提供治疗靶点。
