Ferroptosis, a Potential Therapeutic Target in Alzheimer's Disease.
Ferroptosis, a Potential Therapeutic Target in Alzheimer's Disease.
复制标题
铁死亡，阿尔茨海默病的潜在治疗靶点
DOI：
10.3389/fcell.2021.704298
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhu LQ
中科院分区：
文献类型：
--
作者：
Chen K;Jiang X;Wu M;Cao X;Bao W;Zhu LQ
细胞死亡是阿尔茨海默病（AD）进展过程中的常见现象。然而，引发神经细胞死亡的机制仍不清楚。铁死亡是一种铁依赖性脂质过氧化驱动的细胞死亡，新的证据表明铁死亡参与 AD 的病理过程。此外，AD发病机制的几个标志与铁死亡的特征一致，例如过量的铁积累、脂质过氧化物升高、活性氧（ROS）、还原型谷胱甘肽（GSH）和谷胱甘肽过氧化物酶4（GPX4）水平。此外，一些铁死亡抑制剂可以缓解AD小鼠的AD相关病理症状，并在AD患者中表现出潜在的临床益处。因此，铁死亡逐渐被认为是AD发病机制中独特的细胞死亡机制。但目前仍缺乏直接证据。本文综述了AD中铁死亡的特点、AD病理学的潜在机制，并综述了铁死亡抑制剂在AD临床试验和小鼠/细胞模型中的应用，为未来治疗和预防这种毁灭性疾病提供有价值的信息。
Cell death is a common phenomenon in the progression of Alzheimer’s disease (AD). However, the mechanism of triggering the death of neuronal cells remains unclear. Ferroptosis is an iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Moreover, several hallmarks of AD pathogenesis were consistent with the characteristics of ferroptosis, such as excess iron accumulation, elevated lipid peroxides, and reactive oxygen species (ROS), reduced glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels. Besides, some ferroptosis inhibitors can relieve AD-related pathological symptoms in AD mice and exhibit potential clinical benefits in AD patients. Therefore, ferroptosis is gradually being considered as a distinct cell death mechanism in the pathogenesis of AD. However, direct evidence is still lacking. In this review, we summarize the features of ferroptosis in AD, its underlying mechanisms in AD pathology, and review the application of ferroptosis inhibitors in both AD clinical trials and mice/cell models, to provide valuable information for future treatment and prevention of this devastating disease.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
11
作者：
Ayton, Scott;Wang, Yamin;Bush, Ashley I.
通讯作者：
Bush, Ashley I.
影响因子：
15.1
作者：
Allen M;Zou F;Chai HS;Younkin CS;Miles R;Nair AA;Crook JE;Pankratz VS;Carrasquillo MM;Rowley CN;Nguyen T;Ma L;Malphrus KG;Bisceglio G;Ortolaza AI;Palusak R;Middha S;Maharjan S;Georgescu C;Schultz D;Rakhshan F;Kolbert CP;Jen J;Sando SB;Aasly JO;Barcikowska M;Uitti RJ;Wszolek ZK;Ross OA;Petersen RC;Graff-Radford NR;Dickson DW;Younkin SG;Ertekin-Taner N
通讯作者：
Ertekin-Taner N
DOI：
10.3174/ajnr.a5143
发表时间：
2017-06
期刊：
AJNR. American journal of neuroradiology
影响因子：
--
作者：
Chiang GC;Mao X;Kang G;Chang E;Pandya S;Vallabhajosula S;Isaacson R;Ravdin LD;Alzheimer's Disease Neuroimaging Initiative;Shungu DC
通讯作者：
Shungu DC
影响因子：
5.3
作者：
Cenini G;Sultana R;Memo M;Butterfield DA
通讯作者：
Butterfield DA