Search

α-synuclein (α-syn) is a highly conserved and thermostable protein that is widely distributed in human brain. An intracellular aggregation of α-syn in dopaminergic neurons is the hallmark of a group of neurodegenerative diseases including Parkinson's disease. Interestingly, α-syn is also highly expressed in red blood cells and is considered as one of the most abundant proteins in red blood cells. Moreover, α-syn is thought to play a regulatory role during normal erythropoiesis. However, whether α-syn participates in the pathogenesis of erythroid diseases has not been reported. In this review, we discuss the protein structure of α-syn and the importance of α-syn in erythropoiesis. [ABSTRACT FROM AUTHOR]

The nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor crucial in cellular defense against oxidative and electrophilic stresses. Recent research has highlighted the significance of NRF2 in normal erythropoiesis and anemia. NRF2 regulates genes involved in vital aspects of erythroid development, including hemoglobin catabolism, inflammation, and iron homeostasis in erythrocytes. Disrupted NRF2 activity has been implicated in various pathologies involving abnormal erythropoiesis. In this review, we summarize the progress made in understanding the mechanisms of NRF2 activation in erythropoiesis and explore the roles of NRF2 in various types of anemia. This review also discusses the potential of targeting NRF2 as a new therapeutic approach to treat anemia. [Display omitted] • NRF2 is essential for erythroid homeostasis. • NRF2 protein stability is regulated by interactions with KEAP1 and other factors. • The expression of NRF2 during erythroid development is dynamic. • Targeting NRF2 offers potential therapeutic benefits for anemia treatment. [ABSTRACT FROM AUTHOR]

Ablation of miR‐144/451 disrupts homeostasis of erythropoiesis. Myc, a protooncogenic protein, is essential for erythroblast proliferation but commits rapid downregulation during erythroid maturation. How erythroblasts orchestrate maturation processes through coding and non‐coding genes is largely unknown. In this study, we use miR‐144/451 knockout mice as in vivo model, G1E, MEL erythroblast lines and erythroblasts from fresh mouse fetal livers as in vitro systems to demonstrate that targeted depletion of miR‐144/451 blocks erythroid nuclear condensation and enucleation. This is due, at least in part, to the continued high expression of Myc in erythroblasts when miR‐144/451 is absent. Specifically, miR‐144/451 directly inhibits Myc in erythroblasts. Loss of miR‐144/451 locus derepresses, and thus, increases the expression of Myc. Sustained high levels of Myc in miR‐144/451‐depleted erythroblasts blocks erythroid differentiation. Moreover, Myc reversely regulates the expression of miR‐144/451, forming a positive miR‐144/451‐Myc feedback to ensure the complete shutoff of Myc during erythropoiesis. Given that erythroid‐specific transcription factor GATA1 activates miR‐144/451 and inactivates Myc, our findings indicate that GATA1‐miR‐144/451‐Myc network safeguards normal erythroid differentiation. Our findings also demonstrate that disruption of the miR‐144/451‐Myc crosstalk causes anemia, suggesting that miR‐144/451 might be a potential therapeutic target in red cell diseases. [ABSTRACT FROM AUTHOR]