Platelet lifespan and mechanisms for clearance

After injury, the axon separated from the soma activates an evolutionarily conserved pathway to initiate its degeneration within a day. Attenuation of this pathway results in morphologically preserved severed axons and synapses for weeks after injury. When evoked, these projections remain able to elicit a postsynaptic behavior, a phenomenon that we define as preserved circuit integrity. The mechanism enabling the preservation of circuit integrity is currently unknown. Here we demonstrate that dNmnat-mediated over-expression potently blocks programmed axon degeneration inDrosophila. Thus, severed axons and their synapses of distinct sensory neuron populations remain morphologically preserved and circuit-integrated for at least a week. We used ribosomal pulldown to isolate translatomes from these severed projections. Transcriptional profiling revealed several enriched biological classes. Identified candidates were assessed by the quantification of evoked antennal grooming behavior as proxy for preserved circuit integrity. We identified mediators of local protein synthesis, and specifically candidates involved in protein ubiquitination and calcium homeostasis required for the preservation of circuit integrity by RNAi-mediated knock-down. Our dataset uncovered several uncharacterized genes linked to human disease and may therefore offer insights into avenues for therapeutic treatments.

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Beyond Blood Clotting: The Many Roles of Platelet-Derived Extracellular Vesicles

Muttiah,

Ng,

Lokanathan

et al. 2024

Biomedicines

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Platelet-derived extracellular vesicles (pEVs) are emerging as pivotal players in numerous physiological and pathological processes, extending beyond their traditional roles in hemostasis and thrombosis. As one of the most abundant vesicle types in human blood, pEVs transport a diverse array of bioactive molecules, including growth factors, cytokines, and clotting factors, facilitating crucial intercellular communication, immune regulation, and tissue healing. The unique ability of pEVs to traverse tissue barriers and their biocompatibility position them as promising candidates for targeted drug delivery and regenerative medicine applications. Recent studies have underscored their involvement in cancer progression, viral infections, wound healing, osteoarthritis, sepsis, cardiovascular diseases, rheumatoid arthritis, and atherothrombosis. For instance, pEVs promote tumor progression and metastasis, enhance tissue repair, and contribute to thrombo-inflammation in diseases such as COVID-19. Despite their potential, challenges remain, including the need for standardized isolation techniques and a comprehensive understanding of their mechanisms of action. Current research efforts are focused on leveraging pEVs for innovative anti-cancer treatments, advanced drug delivery systems, regenerative therapies, and as biomarkers for disease diagnosis and monitoring. This review highlights the necessity of overcoming technical hurdles, refining isolation methods, and establishing standardized protocols to fully unlock the therapeutic potential of pEVs. By understanding the diverse functions and applications of pEVs, we can advance their use in clinical settings, ultimately revolutionizing treatment strategies across various medical fields and improving patient outcomes.

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Platelet lifespan and mechanisms for clearance

Cited by 3 publications

References 154 publications

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Beyond Blood Clotting: The Many Roles of Platelet-Derived Extracellular Vesicles

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