PROTACs in platelets: emerging antithrombotic strategies and future perspectives.

Purpose Of Review: Proteolysis-targeted chimeras (PROTACs) are heterobifunctional compounds that selectively target proteins for degradation and are an emerging therapeutic modality to treat diseases such as cancer and neurodegenerative disorders. This review will widen the area of application by highlighting the ability of PROTACs to remove proteins from the anucleate platelets and evaluate their antithrombotic potential.

Recent Findings: Proteomic and biochemical studies demonstrated that human platelets possess the Ubiquitin Proteasomal System as well as the E3 ligase cereblon (CRBN) and therefore may be susceptible to PROTAC-mediated protein degradation.

CryoET reveals actin filaments within platelet microtubules.

Crosstalk between the actin and microtubule cytoskeletons is important for many cellular processes. Recent studies have shown that microtubules and F-actin can assemble to form a composite structure where F-actin occupies the microtubule lumen. Whether these cytoskeletal hybrids exist in physiological settings and how they are formed is unclear.

Difluorinated thromboxane A reveals crosstalk between platelet activatory and inhibitory pathways by targeting both the TP and IP receptors.

Background And Purpose: Thromboxane A (TXA) is a prostanoid produced during platelet activaton, important in enhancing platelet reactivity by activation of TP receptors. However, due to the short half-life, studying TXA signalling is challenging. To enhance our understanding of TP receptor-mediated platelet biology, we therefore synthesised mono and difluorinated TXA analogues and explored their pharmacology on heterologous and endogenously expressed TP receptor function.

Using trials of caloric restriction and bariatric surgery to explore the effects of body mass index on the circulating proteome.

Thousands of proteins circulate in the bloodstream; identifying those which associate with weight and intervention-induced weight loss may help explain mechanisms of diseases associated with adiposity. We aimed to identify consistent protein signatures of weight loss across independent studies capturing changes in body mass index (BMI). We analysed proteomic data from studies implementing caloric restriction (Diabetes Remission Clinical trial) and bariatric surgery (By-Band-Sleeve), using SomaLogic and Olink Explore1536 technologies, respectively.