Long Hui-Zhi, Cheng Yan, Zhou Zi-Wei, Luo Hong-Yu, Wen Dan-Dan, Gao Li-Chen
School of Pharmacy, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China.
Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang, China.
J Neurosci Res. 2022 Jun;100(6):1257-1280. doi: 10.1002/jnr.25033. Epub 2022 Mar 16.
Alzheimer's disease (AD), an age-related neurodegenerative disease, is a striking global health problem. Ferroptosis is a newly discovered form of cell death characterized by iron-dependent lipid peroxidation products and the accumulation of lethal reactive oxygen species. Strict regulation of iron metabolism is essential to ensure neuronal homeostasis. Excess and deficiency of iron are both associated with neurodegeneration. Studies have shown that oxidative stress caused by cerebral iron metabolism disorders in the body is involved in the process of AD, ferroptosis may play an important role in the pathogenesis of AD, and regulating ferroptosis is expected to be a new direction for the treatment of AD. Various organelles are closely related to ferroptosis: mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosome are involved in the regulation of ferroptosis from the aspects of iron metabolism and redox imbalance. In this review, the relationship between AD and the dysfunction of organelles (including mitochondria, endoplasmic reticulum, lysosome, and Golgi apparatus) and the role of organelles in ferroptosis of AD were reviewed to provide insights for understanding the relationship between organelles and ferroptosis in AD and the treatment of AD.
阿尔茨海默病（AD）是一种与年龄相关的神经退行性疾病，是一个引人注目的全球健康问题。铁死亡是一种新发现的细胞死亡形式，其特征是铁依赖性脂质过氧化产物和致命活性氧的积累。严格调节铁代谢对于确保神经元稳态至关重要。铁的过量和缺乏都与神经退行性变有关。研究表明，体内脑铁代谢紊乱引起的氧化应激参与了AD的发病过程，铁死亡可能在AD的发病机制中起重要作用，调节铁死亡有望成为AD治疗的新方向。各种细胞器与铁死亡密切相关：线粒体、内质网、高尔基体和溶酶体从铁代谢和氧化还原失衡方面参与铁死亡的调节。在这篇综述中，综述了AD与细胞器（包括线粒体、内质网、溶酶体和高尔基体）功能障碍之间的关系以及细胞器在AD铁死亡中的作用，为理解AD中细胞器与铁死亡之间的关系以及AD的治疗提供见解。
