Platelet mitochondria, a potent immune mediator in neurological diseases

Abstract

Dysfunction of the immune response is regarded as a prominent feature of neurological diseases, including neurodegenerative diseases, malignant tumors, acute neurotraumatic insult, and cerebral ischemic/hemorrhagic diseases. Platelets play a fundamental role in normal hemostasis and thrombosis. Beyond those normal functions, platelets are hyperactivated and contribute crucially to inflammation and immune responses in the central nervous system (CNS). Mitochondria are pivotal organelles in platelets and are responsible for generating most of the ATP that is used for platelet activation and aggregation (clumping). Notably, platelet mitochondria show marked morphological and functional alterations under heightened inflammatory/oxidative stimulation. Mitochondrial dysfunction not only leads to platelet damage and apoptosis but also further aggravates immune responses. Improving mitochondrial function is hopefully an effective strategy for treating neurological diseases. In this review, the authors discuss the immunomodulatory roles of platelet-derived mitochondria (PLT-mitos) in neurological diseases and summarize the neuroprotective effects of platelet mitochondria transplantation.

Keywords: central nervous system; mitochondria; neuroinflammation; platelet; transplantation.

FIGURE 1

Organelles of platelets and related products. Following activation, platelets show alterations of organelles. Some organelles, such as α-granules, dense granules, lysosomes, and mitochondria, contain multiple substances that can be released from activated platelets.

FIGURE 2

Mitochondrial biological functions in human diseases. Mitochondria affect multiple cellular processes, including inflammation, oxidative stress, autophagy, proliferation/viability, differentiation, necrosis/apoptosis/ferroptosis/pyroptosis/cuproptosis, angiogenesis, and neurogenesis. These cellular processes are closely related to human diseases, including neurological diseases.

FIGURE 3

Signaling pathways and proteins involved in mitochondria-mediated functions. Platelets become hyperactivated upon stimuli from blood under a pathological environment, are released from activated platelets, and act as a damage-associated molecular pattern (DAMP) to stimulate the innate immune system. Mitochondria can exert multiple functions, such as regulating apoptosis and ROS production.