Related Experiment Video
Updated: Jun 21, 2026
09:46
Analyzing Murine Schwann Cell Development Along Growing Axons
Published on: November 21, 2012
Fibrinogen signal transduction in the nervous system
J K Ryu1, D Davalos, K Akassoglou
1Gladstone Institute of Neurological Disease, University of California, San Francisco, CA 94158, USA.
Journal of Thrombosis and Haemostasis : JTH
|July 28, 2009
Summary
Fibrinogen, a blood protein, triggers neuroinflammation and hinders nerve repair after blood-brain barrier (BBB) disruption. Targeting fibrinogen
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Fibrinogen is a key blood protein involved in coagulation, inflammation, and tissue repair.
- It extravasates into the nervous system following injury or disease that compromises the blood-brain barrier (BBB).
- Fibrinogen acts as a direct contributor to neurological disease, not just a marker of BBB disruption.
Purpose of the Study:
- To investigate the causative role of fibrinogen in neurological conditions.
- To elucidate the mechanisms by which fibrinogen mediates its effects in the nervous system.
- To explore therapeutic strategies targeting fibrinogen-receptor interactions in neuroinflammation and neurodegeneration.
Main Methods:
- Examined fibrinogen's function as a ligand for cell-specific receptors in the nervous system.
- Investigated fibrinogen-mediated signaling pathways in microglia via the CD11b/CD18 integrin.
- Analyzed fibrinogen-induced neuronal signaling through the alphavbeta3 integrin and epidermal growth factor (EGF) receptor.
Main Results:
- Fibrinogen activates Akt and Rho signaling in microglia through the CD11b/CD18 integrin.
- Fibrinogen induces epidermal growth factor (EGF) receptor phosphorylation in neurons via the alphavbeta3 integrin.
- Fibrinogen acts as a potent inducer of neuroinflammation and an inhibitor of neurite outgrowth.
Conclusions:
- Fibrinogen plays a direct, causative role in neuroinflammation and impaired neural repair.
- Specific integrin receptors (CD11b/CD18 and alphavbeta3) mediate fibrinogen's detrimental effects in the nervous system.
- Targeting fibrinogen-receptor interactions presents a promising therapeutic avenue for neuroinflammatory and neurodegenerative diseases.
More Related Videos
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:20Extrinsic and Intrinsic Pathways of Hemostasis
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
01:26Signal Transduction: Overview
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...