靶向抑制铁死亡与阿尔茨海默病治疗  

Targeting ferroptosis for treatment of Alzheimer’s disease

作　　者：孙会艳[1,2] 李强 王洪权 SUN Hui-yan;LI Qiang;WANG Hong-quan(Chifeng University Health Science Center,Chifeng Inner Mongolia 024000,China;Key Laboratory of Research on Human Genetic Diseases at University of Inner Mongolia Autonomous Region,Chifeng Inner Mongolia 024000,China;Dept of Neurology,the Affiliated Hospital of Chifeng University,Chifeng Inner Mongolia 024005,China;Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin's Clinical Research Center for Cancer,Tianjin 300060,China)

机构地区：[1]赤峰学院医学部,内蒙古赤峰024000 [2]赤峰学院内蒙古人类遗传病研究自治区高等学校重点实验室,内蒙古赤峰024000 [3]赤峰学院附属医院神经内科,内蒙古赤峰024005 [4]天津医科大学肿瘤医院、天津医科大学肿瘤研究所、国家癌症临床医学研究中心、天津市肿瘤防治重点实验室、天津市恶性肿瘤临床医学研究中心,天津300060

出　　处：《中国药理学通报》2024年第2期229-233,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81260196);内蒙古自然科学基金资助项目(No 2020MS08175,2021MS08131,2021LHMS08024);航天医科科研基金项目(No 2020YK02)。

摘　　要：阿尔茨海默病(Alzheimer’s disease,AD)是一种进行性神经退行性疾病,其病理特征是老年斑和神经原纤维缠结形成。研究表明,大脑区域性铁负荷增加、体内铁平衡失调、氧化应激、蛋白质和脂质氧化均参与AD发病机制。铁死亡是一种新发现的铁依赖性、脂质过氧化驱动的调节性细胞死亡过程,新证据表明铁死亡参与AD的病理过程,而一些针对铁死亡的新化合物能够在AD的细胞和动物模型中对AD显示出具有治疗作用。因此,该文系统总结了铁死亡参与AD发病机制的最新进展,同时重点介绍了以药物靶向抑制铁死亡治疗AD的最新研究进展,为AD的未来治疗和预防提供有价值的信息。Alzheimer’s disease(AD)is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles(NFTs)found in and around pyramidal neurons in cortical tissue.Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress,oxidation of proteins and lipids,and cell death,and appears to be a risk factor for more rapid cognitive decline,thereby involved in multiple aspects of the pathophysiology of AD.Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD.Notably,some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients.This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD,and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.

关 键 词：阿尔茨海默病 铁失衡 脂质过氧化 铁死亡 铁死亡抑制剂 神经保护 

分 类 号：R591.1[医药卫生—内科学] R745.7[医药卫生—临床医学]