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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration
Nature Immunology, Volume 19, No. 11, Year 2018
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Description
Activation of innate immunity and deposition of blood-derived fibrin in the central nervous system (CNS) occur in autoimmune and neurodegenerative diseases, including multiple sclerosis (MS) and Alzheimer’s disease (AD). However, the mechanisms that link disruption of the blood–brain barrier (BBB) to neurodegeneration are poorly understood, and exploration of fibrin as a therapeutic target has been limited by its beneficial clotting functions. Here we report the generation of monoclonal antibody 5B8, targeted against the cryptic fibrin epitope γ 377–395 , to selectively inhibit fibrin-induced inflammation and oxidative stress without interfering with clotting. 5B8 suppressed fibrin-induced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and the expression of proinflammatory genes. In animal models of MS and AD, 5B8 entered the CNS and bound to parenchymal fibrin, and its therapeutic administration reduced the activation of innate immunity and neurodegeneration. Thus, fibrin-targeting immunotherapy inhibited autoimmunity- and amyloid-driven neurotoxicity and might have clinical benefit without globally suppressing innate immunity or interfering with coagulation in diverse neurological diseases. © 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.
Authors & Co-Authors
Ryu, Jae-kyu
United States, San Francisco
Gladstone Institutes
Petersen, Mark Adam
United States, San Francisco
Gladstone Institutes
United States, San Francisco
University of California, San Francisco
Arkin, Michelle R.
United States, San Francisco
University of California, San Francisco
Statistics
Citations: 119
Authors: 3
Affiliations: 8
Identifiers
Doi:
10.1038/s41590-018-0232-x
ISSN:
15292908
Research Areas
Cancer