Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
neuroscience
Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage
Neuron, Volume 96, No. 5, Year 2017
Notification
URL copied to clipboard!
Description
Blood-brain barrier (BBB) disruption alters the composition of the brain microenvironment by allowing blood proteins into the CNS. However, whether blood-derived molecules serve as extrinsic inhibitors of remyelination is unknown. Here we show that the coagulation factor fibrinogen activates the bone morphogenetic protein (BMP) signaling pathway in oligodendrocyte progenitor cells (OPCs) and suppresses remyelination. Fibrinogen induces phosphorylation of Smad 1/5/8 and inhibits OPC differentiation into myelinating oligodendrocytes (OLs) while promoting an astrocytic fate in vitro. Fibrinogen effects are rescued by BMP type I receptor inhibition using dorsomorphin homolog 1 (DMH1) or CRISPR/Cas9 activin A receptor type I (ACVR1) knockout in OPCs. Fibrinogen and the BMP target Id2 are increased in demyelinated multiple sclerosis (MS) lesions. Therapeutic depletion of fibrinogen decreases BMP signaling and enhances remyelination in vivo. Targeting fibrinogen may be an upstream therapeutic strategy to promote the regenerative potential of CNS progenitors in diseases with remyelination failure. Extrinsic inhibitors contribute to remyelination failure in neurological diseases. Petersen et al. identify the blood coagulation factor fibrinogen as an activator of BMP receptor signaling in oligodendrocyte progenitor cells that may be targeted therapeutically to promote remyelination. © 2017 Elsevier Inc.
Authors & Co-Authors
Petersen, Mark Adam
United States, San Francisco
Gladstone Institutes
United States, San Francisco
University of California, San Francisco
Ryu, Jae-kyu
United States, San Francisco
Gladstone Institutes
Lee, Jae K.
United States, Miami
The Miami Project to Cure Paralysis
Lassmann, Hans P.
Austria, Vienna
Medizinische Universität Wien
Rowitch, David H.
United States, San Francisco
University of California, San Francisco
United States, Cambridge
Broad Institute
United Kingdom, Cambridge
University of Cambridge
Statistics
Citations: 113
Authors: 5
Affiliations: 11
Identifiers
Doi:
10.1016/j.neuron.2017.10.008
ISSN:
08966273