The multifaceted role of platelets in mediating brain function

Abstract

Platelets, the small, anucleate blood cells that originate from megakaryocytes in the bone marrow, are typically associated with coagulation. However, it is now apparent that platelets are more multifaceted than originally thought, with their function extending beyond their traditional role in hemostasis to acting as important mediators of brain function. In this review, we outline the broad repertoire of platelet function in the central nervous system, focusing on the similarities between platelets and neurons. We also summarize the role that platelets play in the pathophysiology of various neurological diseases, with a particular focus on neuroinflammation and neurodegeneration. Finally, we highlight the exciting prospect of harnessing the unique features of the platelet proteome and extracellular vesicles, which are rich in neurotrophic, antioxidative, and antiinflammatory factors, for the development of novel neuroprotective and neuroregenerative interventions to treat various neurodegenerative and traumatic pathologies.

Graphical abstract

Figure 1.

Major features and biological cargo of platelets. Platelets contain various organelles and storage granules, including mitochondria, lysosomes, α- and dense granules, a dense tubular system, and a highly invaginated plasma membrane system known as the open canalicular system. The α- and dense granules and lysosomes contain a plethora of small molecules and trophic factors that are released upon activation.

Figure 2.

Platelets and neurons share many similarities. The top panel shows the communication between a presynaptic and a postsynaptic neuron. Neurons are activated by calcium signaling, which triggers the release of neurotransmitters such as serotonin, dopamine, epinephrine, histamine, glutamate, and GABA. The neurotransmitters then bind to the corresponding receptors on the postsynaptic neuron to complete neurotransmission. The lower panel shows an activated platelet with dense granules containing neurotransmitters, adenosine triphosphate, adenosine diphosphate, and calcium, and α-granules containing growth factors, cytokines, antioxidants, and adhesion molecules. Similar to the mechanism which occurs at the presynapse of neurons, calcium-dependent activation of platelets triggers the fusion of the granules with the plasma membrane via highly conserved docking molecules called SNAREs. This results in the rapid release of neurotransmitters, which bind to corresponding receptors expressed on the surface of T cells.