铁死亡在阿尔茨海默病发病机制中的研究进展

Research progress of ferroptosis in pathogenesis of Alzheimer′s disease

【摘要】阿尔茨海默病(AD)是一种与年龄相关的神经退行性疾病,具有病因复杂、患病率高以及病程冗长等特点,给患者家庭乃至整个社会带来了沉重的负担,然而AD的发病机制仍存在较大争议且尚无明确定论。铁死亡作为一种新型的细胞死亡形式,其主要机制是细胞内Fe²⁺浓度升高,破坏了氧化与抗氧化系统的平衡,从而引发活性氧和有毒脂质过氧化物的积累,导致细胞死亡。有研究发现,一些抑制大脑内铁沉积的药物在治疗AD方面展现出了显著的效果,铁死亡可能是导致AD发病的重要原因之一。本文就铁死亡在AD中的发生机制,铁死亡与AD病理的相互作用以及AD中铁死亡的药物治疗3个方面进行综述,旨在为AD的治疗提供新的思考方向。

基金项目:国家老年疾病临床研究中心开放课题(NCRCG-PLAGH-2022002); 科技部重点研发计划(2018YFC1312301); 军队后勤保健课题(21BJZ20); 解放军总医院新技术新业务扶持项目(XYZ-202108)

【Abstract】Alzheimer′s disease (AD), as a neurodegenerative disorder associated with age, presents a complex onset, high prevalence, and a protracted course, and brings a considerable burden and stress to the family and entire society. However, the pathogenesis of AD remains controversial, and there are no definitive conclusions yet. Ferroptosis, a novel form of cell death, is characterized by an increase in intracellular Fe²⁺ concentration, leading to disruption of the balance between oxidative and antioxidative systems, and then resulting in accumulation of reactive oxygen species and toxic lipid peroxidation, and ultimately culminating in cell death. Evidence shows that some drugs that can inhibit brain iron deposition exhibit significant therapeutic effects in treating AD, so ferroptosis is potentially a significant contributor to the onset of AD. In this review, we focus on three themes:the pathogenesis of ferroptosis in AD, the interaction between ferroptosis and AD pathology, and the ferroptosis drug treatment for AD, aiming to provide new thinking orientation for AD treatment strategies.

This work was supported by the Open Project of National Clinical Research Center for Geriatric Diseases (NCRCG-PLAGH-2022002), the Key Research and Development Program of Ministry of Science and Technology of China (2018YFC1312301), the Special Project of Military Logistics Healthcare (21BJZ20) and the Support Project for New Technology and Business of Chinese PLA General Hospital (XYZ-202108).