Targeting Metals in Alzheimer’s Disease: An Update

Issue title: Therapeutic Trials in Alzheimer’s Disease: Where Are We Now?

Guest editors: Paula I. Moreira, Jesus Avila, Daniela Galimberti, Miguel A. Pappolla, Germán Plascencia-Villa, Aaron A. Sorensen, Xiongwei Zhu and George Perry

Article type: Review Article

Authors: Du, Bin^{; 1} | Chen, Kang^{; 1} | Wang, Weiwei | Lei, Peng^{; *}

Affiliations: Department of Neurology and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China

Correspondence: [*] Correspondence to: Dr. Peng Lei, Department of Neurology and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China. E-mail: peng.lei@scu.edu.cn.

Note: [1] These authors contributed equally to this work.

Abstract: One pathological feature of Alzheimer’s disease (AD) is the dysregulated metal ions, e.g., zinc, copper, and iron in the affected brain regions. The dysregulation of metal homeostasis may cause neurotoxicity and directly addressing these dysregulated metals through metal chelation or mitigating the downstream neurotoxicity stands as a pivotal strategy for AD therapy. This review aims to provide an up-to-date comprehensive overview of the application of metal chelators and drugs targeting metal-related neurotoxicity, such as antioxidants (ferroptotic inhibitors), in the context of AD treatment. It encompasses an exploration of their pharmacological effects, clinical research progress, and potential underlying mechanisms.

Keywords: Alzheimer’s disease, copper, ferroptosis, iron, metal chelators, zinc

DOI: 10.3233/JAD-240140

Journal: Journal of Alzheimer's Disease, vol. 101, no. s1, pp. S141-S154, 2024