Is eryptosis druggable?

Excerpt

Regulated cell death (RCD) modalities such as necroptosis, pyroptosis, ferroptosis, or cuproptosis have been extensively studied as a target for cancer therapy due to their ability to ensure cell death in apoptosis-resistant tumors or to modulate tumor microenvironment through emitting multiple immunogenic signals by dying cells [1, 2]. Recent progress in the field of RCD has contributed to unraveling the landscape of cell death processes in particular cell types. For instance, there is accumulating evidence that erythrocytes display a limited set of RCD pathways undergoing senescence, eryptosis, and necroptosis [3‐6]. A recent review has demonstrated that eryptosis of mature erythrocytes differs from apoptosis of nucleated cells at the level of crucial signaling pathways [7]. This is a prerequisite condition for developing eryptosis-specific pharmaceutical modulators. Overall, eryptosis is a controlled RCD of mature erythrocytes associated with cell shrinkage, membrane blebbing and phospholipid scrambling mediated primarily by intracellular Ca²⁺ elevation, reactive oxygen species (ROS) and ceramide accumulation [3, 6]. Clinically, accelerated eryptosis may result in anemia. Eryptosis-associated anemia has been reported in elderly individuals, acute cardiac failure, end stage renal disease, hypertension, metabolic syndrome, diabetes mellitus type 2, systemic lupus erythematosus, arteritis, lung cancer, etc. Thus, therapeutic interventions aiming to reduce eryptosis might be beneficial. …