Schreiner Oliver Daniel, Schreiner Thomas Gabriel
Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.
Medical Oncology Department, Regional Institute of Oncology, Iasi, Romania.
Front Aging. 2023 Aug 2;4:1234958. doi: 10.3389/fragi.2023.1234958. eCollection 2023.
Neurodegenerative disorders, particularly Alzheimer's disease (AD), remain a great challenge regarding the finding of effective treatment, one main reason being the incomplete understanding of their etiology. With many intensely debated hypotheses, a newer approach based on the impact of iron imbalance in sustaining neurodegeneration in the central nervous system becomes increasingly popular. Altered iron homeostasis leads to increased iron accumulation in specific brain areas, explaining the clinical picture of AD patients. Moreover, growing evidence sustains the significant impact of iron metabolism in relationship to other pathological processes encountered in the AD-affected brain, such as the amyloidogenic pathway, chronic inflammation, or oxidative stress. In this context, this mini-review aims to summarize the novel data from the continuously expanding literature on this topic in a didactic manner. Thus, in the first part, the authors briefly highlight the most relevant aspects related to iron absorption, transport, regulation, and elimination at the cerebral level, focusing on the role of the blood-brain barrier and the newer concept of ferroptosis. Subsequently, currently available iron chelation therapies are discussed, including an overview of the most relevant clinical trials on this topic. In the final part, based on the latest results from and studies, new research directions are suggested to enhance the development of effective antidementia therapies.
神经退行性疾病,尤其是阿尔茨海默病(AD),在寻找有效治疗方法方面仍然是一个巨大的挑战,一个主要原因是对其病因的认识不完整。有许多激烈争论的假说,一种基于铁失衡在维持中枢神经系统神经退行性变中的影响的新方法越来越受欢迎。铁稳态的改变导致特定脑区铁积累增加,这解释了AD患者的临床表现。此外,越来越多的证据支持铁代谢与AD受累大脑中遇到的其他病理过程之间的重大影响,如淀粉样蛋白生成途径、慢性炎症或氧化应激。在此背景下,本综述旨在以教学的方式总结关于该主题的不断扩展的文献中的新数据。因此,在第一部分,作者简要强调了与大脑水平上的铁吸收、运输、调节和清除相关的最相关方面,重点关注血脑屏障的作用和铁死亡的新概念。随后,讨论了目前可用的铁螯合疗法,包括对该主题最相关临床试验的概述。在最后一部分,基于[具体研究]和[具体研究]的最新结果,提出了新的研究方向,以促进有效抗痴呆疗法的发展。