REVIEW article
Front. Pharmacol.
Sec. Neuropharmacology
Ferroptosis in Diabetes-Associated Cognitive Dysfunction: Mechanisms and Therapeutic Potential
Liu Hang 1
SiQi Qian 1
Shuzhen Liu 1
Wenbiao Xiao 1
Yijie You 2
Yi Zeng 1
1. The Second Xiangya Hospital of Central South University, Changsha, China
2. Central South University Xiangya School of Medicine, Changsha, China
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Abstract
Diabetic-Associated Cognitive Dysfunction (DACD) is a major central nervous system complication of diabetes. Its pathogenesis involves dysfunction of the neurovascular unit, oxidative stress, and chronic neuroinflammation. Ferroptosis, an iron-dependent form of regulated cell death, is strongly implicated in DACD progression. This review synthesizes its core mechanisms, focusing on three key areas: metabolic iron overload, aberrant lipid peroxidation, and disruptions in key amino acid pathways. These processes collectively driveferroptotic damage in vulnerable neurons of the hippocampus and cortex, ultimately leading to cognitive decline. Furthermore, this work highlights the translational potential of targeting ferroptosis using specific inhibitors (e.g., Ferrostatin-1, Deferoxamine, Erythropoietin) for DACD treatment, offering novel strategic insights for intervention. Future clinical investigations are essential to validate the efficacy of these therapeutic targets in diabetic patient populations.
Summary
Keywords
diabetic-associated cognitive dysfunction, ferroptosis, iron metabolism, Lipid Peroxidation, Pathogenesis, Therapeutic target
Received
28 November 2025
Accepted
19 February 2026
Copyright
© 2026 Hang, Qian, Liu, Xiao, You and Zeng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Yi Zeng
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