Abstract Number: PB1744
Meeting: ISTH 2020 Congress
Background: When prion, gets misfolded into infectious scrapie isoform (PrPs), primarily a β-pleated insoluble fibril, it forms aggregates in the extracellular matrix that leads to non-treatable neurodegenerative disease. We demonstrated earlier that human plasma fibrinogen interacts with the amyloid β (Aβ), whose structure resembles PrPs, and prevents Aβ-induced human platelet activation and neurotoxicity. We have also shown that PrPs induces a prothrombotic state in vitro by stimulating platelets. This led us to explore whether fibrinogen interaction with the prion peptide also attenuates PrPs-induced toxicity to neuronal cells and human platelets.
Aims: To explore interaction of fibrinogen with PrPs and to study the effects of this interaction on prion-mediated neuronal cell toxicity and human platelet activation.
Methods: Neuroblastoma SH-SY5Y cells were cultured in DMEM/F12 media. Platelets were isolated from fresh human blood with consent from healthy volunteers, as approved by the Institutional Ethical Committee of IMS, BHU, Varanasi, India. The study complied with the Declaration of Helsinki. Surface plasmon resonance, confocal microscopy, and scanning electron microscopy were used to study the interaction between PrPs and fibrinogen. To assess cell viability and cell signaling in human platelets and neuronal cells, cell viability assay, measurement of cytosolic free Ca2+, calpain activity assay, immunoblotting, extracellular vesicle (EVs) release, measurement of mitochondrial membrane potential, were carried out. Two-tailed Student’s t-test was employed for the evaluation of significance.
Results: A significant interaction was found between plasma fibrinogen and PrPs. Fibrinogen upon interaction with PrPs attenuated prion peptide-induced rise in intracellular Ca2+, shedding of EVs, calpain activity and proteolysis of talin in platelets. Fibrinogen also prevented toxic effects of PrPs on viability, morphology and mitochondrial function of neuronal cells.
Conclusions: Plasma fibrinogen acts as a natural deterrent for prion-induced Neurotoxicity and human platelet activation.
To cite this abstract in AMA style:Gautam D, Chaurasia RN, Dash D. Plasma Fibrinogen Interaction with Prion Peptide Mitigates Prion-Mediated Neuronal Cell Toxicity And Human Platelet Activation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/plasma-fibrinogen-interaction-with-prion-peptide-mitigates-prion-mediated-neuronal-cell-toxicity-and-human-platelet-activation/. Accessed January 21, 2022.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/plasma-fibrinogen-interaction-with-prion-peptide-mitigates-prion-mediated-neuronal-cell-toxicity-and-human-platelet-activation/