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.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Fibrin promotes oxidative stress and neuronal loss in traumatic brain injury via innate immune activation
Journal of Neuroinflammation Open Access 15 April 2024
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Petersen, M. A., Ryu, J. K. & Akassoglou, K. Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics. Nat. Rev. Neurosci. 19, 283–301 (2018). This review highlights fibrinogen functions in neurological diseases.
Iadecola, C. The pathobiology of vascular dementia. Neuron 20, 844–866 (2013). This review highlights vascular and immune mechanisms in Alzheimer’s disease.
Hajishengallis, G., Reis, E. S., Mastellos, D. C., Ricklin, D. & Lambris, J. D. Novel mechanisms and functions of complement. Nat. Immunol. 18, 1288–1298 (2017). This review highlights complement functions in immunity and disease.
Mendiola, A. S. et al. Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation. Nat. Immunol. 21, 513–524 (2020). This article reports Tox-seq transcriptomics and the discovery of selective innate immune cell inhibitors.
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.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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).
Rights and permissions
About this article
Cite this article
Fibrin induces neurotoxic microglia gene programs in neurodegeneration. Nat Immunol 24, 1062–1063 (2023). https://doi.org/10.1038/s41590-023-01542-w
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41590-023-01542-w
This article is cited by
-
Fibrin promotes oxidative stress and neuronal loss in traumatic brain injury via innate immune activation
Journal of Neuroinflammation (2024)