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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Signaling
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1534235
Prion protein fragment (106–126) activates NLRP3 inflammasome and promotes platelet-monocyte/neutrophil interactions, potentially contributing to an inflammatory state
Provisionally accepted- Banaras Hindu University, Varanasi, India
Prion diseases are neurodegenerative disorders where infectious prion proteins (PrP) featuring an amyloidogenic amino acid sequence, PrP (106–126), accumulate in the brain leading to neuroinflammation while it can also access circulation by breaching the blood-brain barrier. Platelets are highly sensitive cells in blood, which have been widely employed as ‘peripheral’ model for neurons. In addition to their stellar roles in hemostasis and thrombosis, platelets are also known to function as immune cells and possess necessary components of functional inflammasome. This study demonstrates that prion proteins drive inflammasome assembly in platelets and upregulate activity of caspase-1, a critical readout of functional inflammasomes. Inflammasome activation is fuelled by reactive oxygen species (ROS) generated in prion-stimulated platelets that eventually leads to formation of platelet-monocyte/neutrophil aggregates, which was prohibited by small-molecule inhibitors of either caspase-1 or ROS. Thus, in addition to their neurotoxic effects on neuronal cells and stimulation of pro-coagulant activity in platelets, prions also unleash an inflammatory response in the organism.
Keywords: prion, platelets, NLRP3 inflammasome, Platelet-monocyte/neutrophil interaction, ROS, EGCG
Received: 25 Nov 2024; Accepted: 10 Feb 2025.
Copyright: © 2025 Verma, Dash, Kailashiya, Mukherjee and Chaurasia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Debabrata Dash, Banaras Hindu University, Varanasi, India
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