铁死亡对阿尔茨海默病的影响及药物研究进展

Impact of Ferroptosis on Alzheimer’s Disease and Its Drug Research Progress

阿尔茨海默病(AD)是一种慢性中枢神经系统退行性疾病。铁死亡是近年来发现的新型铁依赖性细胞死亡形式,典型特征为铁积累过多、谷胱甘肽过氧化物酶4失活、活性氧和脂质过氧化物升高。近年来的证据表明,铁死亡在AD的病理过程中起重要作用,但其具体机制尚不清楚。本文综述了铁平衡失调导致老年斑和神经元纤维缠结、加剧神经炎症以及介导神经细胞死亡等潜在相互作用,并总结了铁螯合剂、抗氧化剂以及铁死亡调节因子等针对铁死亡相关的AD治疗策略,以期为AD诊断和治疗提供有价值的信息。

Alzheimer’s disease(AD)is a chronic degenerative condition affecting the central nervous system and is the most prevalent form of senile dementia.Unfortunately,it remains incurable at present.In recent years,a novel iron-dependent form of cell death called ferroptosis has been identified.This process is characterized by an excess of iron accumulation,inactivation of glutathione peroxidase 4,and elevated levels of reactive oxygen species and lipid peroxides.Recent evidence indicates that ferroptosis plays an important role in the pathological process of AD,but its specific mechanism is still unclear.This article reviews the potential interactions of iron imbalance leading to senile plaque and neurofibrillary tangles,aggravating neuroinflammation,and mediating neuronal cell death.In addition,this article summarizes the AD treatment strategies related to ferroptosis,such as iron chelators,antioxidants and ferroptosis regulators,to provide valuable information for the diagnosis and treatment of AD in the future.