Abstract
Parkinson’s disease (PD) presents a challenge, with neuroinflammation and immune dysregulation central to its pathogenesis. This review examines TREM2—a microglial receptor governing phagocytosis, metabolic adaptation, and immune phenotypes—as an important orchestrator of innate immunity across PD, with roles that appear stage- and context-dependent. We synthesize structure, signaling, and heterogeneity; integrate single-cell multi-omics, animal models, and clinical data; outline conserved mechanisms; and consider translational implications as an investigational biomarker and therapeutic target, emphasizing spatiotemporal dynamics.
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Acknowledgements
This work was partially supported by the National Natural Science Foundation of China (32161143021, 81271410) and the Natural Science Foundation of Henan Province (182300410313).
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K.H. and Y.X. conceived the title, prepared the initial draft, and designed the figures. Z.A. and J.W. (Jing Wang), and M.Z. assisted in drafting and revising the manuscript, and preparing the final version. Y.L., K.H., X.Z., and J.W. (Jianshe Wei) helped prepare the final manuscript, critically revised the manuscript, and supervised the project. All authors read and approved the final manuscript.
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Hou, K., An, Z., Xu, Y. et al. Parkinson’s disease: spatiotemporal regulation and therapeutic prospects of TREM2-mediated microglial responses. npj Parkinsons Dis. (2026). https://doi.org/10.1038/s41531-025-01247-x
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DOI: https://doi.org/10.1038/s41531-025-01247-x
