Abstract
The blood coagulation protein fibrinogen is deposited in the brain in a wide range of neurological diseases and traumatic injuries with blood–brain barrier (BBB) disruption. Recent research has uncovered pleiotropic roles for fibrinogen in the activation of CNS inflammation, induction of scar formation in the brain, promotion of cognitive decline and inhibition of repair. Such diverse roles are possible in part because of the unique structure of fibrinogen, which contains multiple binding sites for cellular receptors and proteins expressed in the nervous system. The cellular and molecular mechanisms underlying the actions of fibrinogen are beginning to be elucidated, providing insight into its involvement in neurological diseases, such as multiple sclerosis, Alzheimer disease and traumatic CNS injury. Selective drug targeting to suppress the damaging functions of fibrinogen in the nervous system without affecting its beneficial effects in haemostasis opens a new fibrinogen therapeutics pipeline for neurological disease.
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Acknowledgements
The authors are grateful to L. Mucke and D. Reich for critical reading of the manuscript, T. Roberts and J. Carroll for graphics and G. Howard for editorial assistance. The authors are supported by the US National Institutes of Health (NIH), National Institute of Child Health and Human Development (NICHD) K12-HD072222 grant and a Pediatric Scientist Development Program fellowship (supported by March of Dimes 4-FY10-461 and NIH/NICHD K12-HD000850) to M.A.P, a Race to Erase MS Young Investigator Award and American Heart Association Scientist Development grant to J.K.R and the National Multiple Sclerosis Society grant RG4985, NIH/NINDS grant R35 NS097976, the Conrad N. Hilton Foundation grant and US Department of Defense MS160082 grant to K.A.
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K.A., M.A.P. and J.K.R. researched data for the article, made substantial contributions to the discussion of content and contributed to the writing, review and editing of the manuscript before submission.
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K.A. is a co-founder of MedaRed. K.A. and J.K.R. are named inventors in patents and patent applications. Their interests are managed by the Gladstone Institutes in accordance with its conflict of interest policy.
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Petersen, M., Ryu, J. & Akassoglou, K. Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics. Nat Rev Neurosci 19, 283–301 (2018). https://doi.org/10.1038/nrn.2018.13
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DOI: https://doi.org/10.1038/nrn.2018.13
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