Extravasation of blood into the brain and activation of innate immune cells are hallmarks and therapeutic targets in neurological diseases. We show that specific blood proteins induce distinct receptor-mediated gene programs in microglia and that the blood coagulation protein fibrin has a causal role in pathogenic innate immunity in models of neurological diseases.
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References
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Merlini, M. et al. Fibrinogen induces microglia-mediated spine elimination and cognitive impairment in Alzheimer’s disease. Neuron 101, 1099-1108. Neuron 101, 1099–1108 (2019). This article reports that fibrin signaling is necessary for synaptic dysfunction and cognitive impairment in Alzheimer’s disease models.
Ryu, J. K. et al. Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration. Nat. Immunol. 19, 1212–1223 (2018). This article reports fibrin-targeting immunotherapy to suppress disease in MS and Alzheimer’s disease models.
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This is a summary of: Mendiola, A. S. et al. Defining blood-induced microglia functions in neurodegeneration through multiomic profiling. Nat. Immunol. https://doi.org/10.1038/s41590-023-01522-0 (2023).
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Fibrin induces neurotoxic microglia gene programs in neurodegeneration. Nat Immunol 24, 1062–1063 (2023). https://doi.org/10.1038/s41590-023-01542-w
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DOI: https://doi.org/10.1038/s41590-023-01542-w
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Fibrin promotes oxidative stress and neuronal loss in traumatic brain injury via innate immune activation
Journal of Neuroinflammation (2024)
