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The role of microglia in neurodegenerative diseases: from the perspective of ferroptosis

Acta Pharmacologica Sinica (2025)Cite this article

Abstract

Iron plays a pivotal role in numerous fundamental biological processes in the brain. Among the various cell types in the central nervous system, microglia are recognized as the most proficient cells in accumulating and storing iron. Nonetheless, iron overload can induce inflammatory phenotype of microglia, leading to the production of proinflammatory cytokines and contributing to neurodegeneration. A growing body of evidence shows that disturbances in iron homeostasis in microglia is associated with a range of neurodegenerative disorders. Recent research has revealed that microglia are highly sensitive to ferroptosis, a form of iron-dependent cell death. How iron overload influences microglial function? Whether disbiosis in iron metabolism and ferroptosis in microglia are involved in neurodegenerative disorders and the underlying mechanisms remain to be elucidated. In this review we focus on the recent advances in research on microglial iron metabolism as well as ferroptosis in microglia. Meanwhile, we provide a comprehensive overview of the involvement of microglial ferroptosis in neurodegenerative disorders from the perspective of crosstalk between microglia and neuron, with a focus on Alzheimer’s disease and Parkinson’s disease.

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Fig. 1
Fig. 2: Reported factors affecting microglial ferroptosis.
Fig. 3: The crosstalk between microglia and neuron.
Fig. 4: The crosstalk between microglia and neuron.
Fig. 5: Microglial ferroptosis in PD.
Fig. 6: Microglial ferroptosis in AD.

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Acknowledgements

This study is supported by grants from the National Natural Science Foundation of China (32200802, 32371187, 32170984), Qingdao West Coast New District Science and Technology Project (2020-3-2), Excellent Innovative Team of Shandong Province (2020KJK007), and Taishan Scholars Construction Project, Shandong.

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Authors and Affiliations

  1. Institute of Brain Science and Disease, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao, 266071, China

    Ying-juan Liu, Guo-rui Jia, Sheng-han Zhang, Yun-liang Guo, Hua-min Xu & Jun-xia Xie

  2. Department of Physiology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China

    Guo-rui Jia, Sheng-han Zhang & Hua-min Xu

  3. College of Life Sciences and Health, University of Health and Rehabilitation Science, Qingdao, 266113, China

    Xi-zhen Ma

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Liu, Yj., Jia, Gr., Zhang, Sh. et al. The role of microglia in neurodegenerative diseases: from the perspective of ferroptosis. Acta Pharmacol Sin (2025). https://doi.org/10.1038/s41401-025-01560-4

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