Related Experiment Video
Updated: Sep 27, 2025
Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
Published on: March 12, 2018
Fibrinogen Mitigates Prion-Mediated Platelet Activation and Neuronal Cell Toxicity
Deepa Gautam1,2, Jyotsna Kailashiya1, Arundhati Tiwari1
1Center for Advanced Research on Platelet Signaling and Thrombosis Biology, Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Abstract:
Prion peptide (PrP) misfolds to infectious scrapie isoform, the β pleat-rich insoluble fibrils responsible for neurodegeneration and fatal conformational diseases in humans. The amino acid sequence 106-126 from prion proteins, PrP(106-126), is highly amyloidogenic and implicated in prion-induced pathologies. Here, we report a novel interaction between PrP(106-126) and the thrombogenic plasma protein fibrinogen that can lead to mitigation of prion-mediated pro-thrombotic responses in human platelets as well as significant decline in neuronal toxicity. Thus, prior exposure to fibrinogen-restrained PrP-induced rise in cytosolic calcium, calpain activation, and shedding of extracellular vesicles in platelets while it, too, averted cytotoxicity of neuronal cells triggered by prion peptide. Interestingly, PrP was found to accelerate fibrin-rich clot formation, which was resistant to plasmin-mediated fibrinolysis, consistent with enhanced thrombus stability provoked by PrP. We propose that PrP-fibrinogen interaction can be clinically exploited further for prevention and management of infectious prion related disorders. Small molecules or peptides mimicking PrP-binding sites on fibrinogen can potentially mitigate PrP-induced cellular toxicity while also preventing the negative impact of PrP on fibrin clot formation and lysis.
Insights
Prion peptide (PrP) interacts with fibrinogen, reducing neuronal toxicity and platelet pro-thrombotic responses. This novel interaction may offer therapeutic strategies for prion diseases.
Area of Science:
- Neuroscience
- Biochemistry
- Hematology
Background:
- Prion diseases involve misfolded prion protein (PrP) forming amyloid fibrils.
- Prion peptide (PrP) sequence 106-126 is amyloidogenic and linked to prion pathologies.
- PrP is associated with pro-thrombotic effects and neuronal toxicity.
Purpose of the Study:
- To investigate the interaction between PrP(106-126) and fibrinogen.
- To determine the effect of this interaction on platelet responses and neuronal toxicity.
- To explore the impact of PrP on fibrin clot formation and stability.
Main Methods:
- Studied the interaction between PrP(106-126) and fibrinogen.
- Assessed PrP-fibrinogen effects on platelet cytosolic calcium, calpain activation, and extracellular vesicle shedding.
- Evaluated the impact of PrP-fibrinogen on neuronal cell cytotoxicity.
- Analyzed PrP's effect on fibrin clot formation and resistance to plasmin-mediated fibrinolysis.
Main Results:
- Fibrinogen mitigated PrP-induced increases in platelet cytosolic calcium, calpain activation, and extracellular vesicle shedding.
- Fibrinogen exposure averted PrP-induced neuronal cell toxicity.
- PrP accelerated fibrin clot formation, resulting in clots resistant to fibrinolysis.
- These findings suggest enhanced thrombus stability due to PrP.
Conclusions:
- The interaction between PrP and fibrinogen can mitigate PrP-induced cellular toxicity and pro-thrombotic responses.
- This interaction may be clinically relevant for managing prion-related disorders.
- Developing molecules that mimic PrP-binding sites on fibrinogen could be a therapeutic strategy.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
01:16Clot Retraction and Fibrinolysis
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins