Open Access

Mechanism of action and therapeutic potential of S100A8/A9 in neuroinflammation and cognitive impairment: From molecular target to clinical application (Review)

  • Authors:
    • Xilong Guan
    • Linan Zha
    • Xiaoling Zhu
    • Xiuqin Rao
    • Xiangfei Huang
    • Yanhong Xiong
    • Youwei Guo
    • Mojiao Zhang
    • Dongshan Zhou
    • Qikun Tu
    • Jianhang Wu
    • Xifeng Wang
    • Fuzhou Hua
    • Jing Xu
  • View Affiliations

  • Published online on: July 16, 2025     https://doi.org/10.3892/ijmm.2025.5588
  • Article Number: 147
  • Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The complex of proteins S100A8/A9 has been recognized as a major initiator of cognitive disorder onset, including, but not restricted to, neuroinflammation. Cognitive impairment or decline in memory, attention and executive function has been on the rise and is a major public health priority. Several neurological conditions that affect the brain and cognitive processes, including central nervous system diseases such as Alzheimer's disease and stroke, and systemic diseases, such as sepsis and systemic lupus erythematosus, are associated with S100A8/A9. Experiments have progressively demonstrated that S100A8/A9 plays a role in cognitive decline, as it regulates cognitive domains, including sleep, learning, memory, and emotion control, via several mechanisms. In this review, a critical overview of the role of S100A8/A9 in the treatment of neurocognitive diseases is provided, including the regulation of brain function and the pathogenesis of diseases, and potential novel therapies are suggested. It is necessary to study S100A8/A9 alone as an alternative marker for the diagnosis and treatment of neurocognitive diseases, and in line with the requirements of therapy for cognitive impairment. As S100A8/A9 research continues, the understanding and treatment of neurocognitive diseases may improve.
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October-2025
Volume 56 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
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Spandidos Publications style
Guan X, Zha L, Zhu X, Rao X, Huang X, Xiong Y, Guo Y, Zhang M, Zhou D, Tu Q, Tu Q, et al: Mechanism of action and therapeutic potential of S100A8/A9 in neuroinflammation and cognitive impairment: From molecular target to clinical application (Review). Int J Mol Med 56: 147, 2025.
APA
Guan, X., Zha, L., Zhu, X., Rao, X., Huang, X., Xiong, Y. ... Xu, J. (2025). Mechanism of action and therapeutic potential of S100A8/A9 in neuroinflammation and cognitive impairment: From molecular target to clinical application (Review). International Journal of Molecular Medicine, 56, 147. https://doi.org/10.3892/ijmm.2025.5588
MLA
Guan, X., Zha, L., Zhu, X., Rao, X., Huang, X., Xiong, Y., Guo, Y., Zhang, M., Zhou, D., Tu, Q., Wu, J., Wang, X., Hua, F., Xu, J."Mechanism of action and therapeutic potential of S100A8/A9 in neuroinflammation and cognitive impairment: From molecular target to clinical application (Review)". International Journal of Molecular Medicine 56.4 (2025): 147.
Chicago
Guan, X., Zha, L., Zhu, X., Rao, X., Huang, X., Xiong, Y., Guo, Y., Zhang, M., Zhou, D., Tu, Q., Wu, J., Wang, X., Hua, F., Xu, J."Mechanism of action and therapeutic potential of S100A8/A9 in neuroinflammation and cognitive impairment: From molecular target to clinical application (Review)". International Journal of Molecular Medicine 56, no. 4 (2025): 147. https://doi.org/10.3892/ijmm.2025.5588