Platelets: The Unexpected Players in Protein Degredation

( Platelets, from Williams, 2021)

Your DNA, while an incredible tool that helps humans and other organisms survive and adapt, can make mistakes sometimes. Proteins in the body can be made of the wrong amino acids that your DNA helps to make. As a result, the protein can be a defect, which can cause serious harm to your body and potentially others. Fortunately, your body has a built-in mechanism to stop the proteins from causing harm: protein degradation. When defunct proteins are degrading, they basically break apart, either slowly on their own or with the help of catalysts. However, some harmful or useless proteins don’t degrade as easily as others. As a result, researchers have managed to find another way: platelets.

How do we degrade proteins?

Other than platelets,your body and medical professionals use other methods to naturally and artificially degrade harmful proteins. Lysosomes (organelles in your cells that dispose of waste) have multiple ways to do it. In macroautophagy, defunct proteins are recognized and engulfed, where they fuse with lysosomes and get degraded. In microautophagy, lysosomes degrade the protein directly, without any third agent. However, lysosomes can only do this with extracellular proteins, and can’t deal with proteins inside only one cell. That’s where platelets come in.

Platelets are cell fragments in your blood whose primary purpose is to stop bleeding. They help clot the blood, so more blood can’t get out and the body can heal more easily. In addition, they also contain a large protein complex called the proteasome that degrades proteins. When proteins misfold, they usually produce amyloid, which is an insoluble buildup. Amyloid alerts the platelet of a problem, which it fixes. The proteasome can help shred proteins back into amino acids, which can then be used for other purposes. In addition, they can also do this for proteins that only work within a cell, so misfolded proteins that harm on a cellular level can be erased. The body naturally does this, but platelets can be modified to do this more effectively.

How does this help us?

This rather new technology has already shown promise in trials, and just might be essential to future medicine. For instance, one way to stop breast cancer is to perform surgery. However, recurrence is common after the surgery. Thus, platelets’ natural tendency to heal post-surgical sites can be taken advantage of, and used to degrade proteins that help tumors survive. In addition to fighting cancer survival, they might be able to degrade proteins that cause neurodegenerative diseases, like Alzheimer's and Huntington's disease. 

When you consider the effect conditions like cancer and Alzheimer's have on actual lives, lysosomes and platelets suddenly seem a lot more important to human health. These natural processes can be modified to be even more effective, and save lives in the process.

References

Eszter Herczenik, Bouma, B., Korporaal, S. J. A., Remo Strangi, Zeng, Q., Gros, P., Eck, M. V., J.C, T., Martijn F.B.G. Gebbink, & Akkerman, J.-W. N. (2007). Activation of Human Platelets by Misfolded Proteins. Arteriosclerosis Thrombosis and Vascular Biology, 27(7), 1657–1665. https://doi.org/10.1161/atvbaha.107.143479

‌Zhao, L., Zhao, J., Zhong, K., Tong, A., & Jia, D. (2022). Targeted protein degradation: mechanisms, strategies and application. Signal Transduction and Targeted Therapy, 7(1). https://doi.org/10.1038/s41392-022-00966-4

kgerhards. (2024, December 12). Platelets as Protein Degraders - School of Pharmacy. School of Pharmacy. https://pharmacy.wisc.edu/2024/12/12/platelets-as-protein-degraders/

‌Kraemer, B. F., Lindemann, S., & Weyrich, A. S. (2013). Protein degradation systems in platelets. Thrombosis and Haemostasis, 110(11), 920–924. https://doi.org/10.1160/th13-03-0183

‌Williams, M. (2021). What are Platelets and Why are They Important? Www.hopkinsmedicine.org. https://www.hopkinsmedicine.org/health/conditions-and-diseases/what-are-platelets-and-why-are-they-important

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