One immune cell to bind them all: platelet contribution to neurodegenerative disease

Fig. 1. Receptors Expressed on Activated Platelet Cell Surface. The figure illustrates the main receptors expressed on the cell surface of platelets, including Toll-like receptor 2 (TLR-2), Toll-like receptor 4 (TLR-4), TREM-like transcript 1 (TLT-1), platelet glycoprotein 4 (CD36), (GP)Ib-IX-V, C-type lectin-like receptor 2 (CLEC-2, CLEC-1b), P2Y12, P2 × 1, P2Y1, Piezo 1, GPVI, PAR1, PAR3, PAR4, αvβ3, α2β1, α5β1, CD352, CD244/2B4, PECAM-1 CD84, CEACAM1, CEACAM2, (GP)IIb/IIIa, CD150, α6β1, CD48, A2A Adenosine receptor, and several of their key agonists in inflammation including Damage-associated molecular pattern molecules (DAMPs), Pathogen-associated molecular patterns (PAMPs), Fibrinogen, Fibronectin, Laminin, vWF, Collagen, Constant Fragment of Immunoglobulin G, Thrombin, Vitronectin, and Podoplanin expressed by Lymphatic endothelial cells (LECs). Furthermore, the formation of PMVs and the exocytosis of soluble molecules from platelet granules are highlighted on the left-hand side of the figure

Fig. 2. Dynamic Impact of Platelet Activation and Subsequent Granular Content Release. The figure depicts the anatomy and contents of both inactivated and activated platelets, highlighting the common mechanisms of platelet activation, including chemokine/cytokine detection, receptor ligand binding, and mechanosensation. Following activation platelets release, a wide variety of soluble factors from various internal granules that influence their surrounding environment. These factors have the potential to induce broad systemic and local effects on inflammation. They can promote immune cell recruitment to inflammatory sites, induce systemic inflammation by secreting platelet cytokines and chemokines, and facilitate platelet infiltration into the parenchyma surrounding blood vessels through breaks in the BBB. This process may activate additional platelets and exacerbate dysregulation in disease states such as AD

Fig. 3. Overview of Platelet Activity in blood vessel from neurodegenerative conditions. The figure depicts platelets in the vascular environment, highlighting the diversity of interactions they can participate in including platelet-neutrophil, platelet-endothelial, and platelet-platelet crosstalk. Additionally, breakdown of the blood-brain barrier and potential platelet infiltration is shown. The inlets highlight the most prominent receptor ligand bindings that occur in platelet-neutrophil, platelet-endothelial, and platelet-platelet crosstalk, from left to right, in inflammation