Therapeutic Relevance of Inducing Autophagy in β-Thalassemia

The beta-thalassemias are inherited genetic disorders affecting the hematopoietic system. In beta-thalassemias, more than 350 mutations of the adult beta-globin gene cause the low or absent production of adult hemoglobin (HbA). A clinical parameter affecting the physiology of erythroid cells is the excess of free alpha-globin. Possible experimental strategies for a reduction in excess free alpha-globin chains in beta-thalassemia are CRISPR-Cas9-based genome editing of the beta-globin gene, forcing "de novo" HbA production and fetal hemoglobin (HbF) induction. In addition, a reduction in excess free alpha-globin chains in beta-thalassemia can be achieved by induction of the autophagic process. This process is regulated by the Unc-51-like kinase 1 (Ulk1) gene. The interplay with the PI3K/Akt/TOR pathway, with the activity of the alpha-globin stabilizing protein (AHSP) and the involvement of microRNAs in autophagy and Ulk1 gene expression, is presented and discussed in the context of identifying novel biomarkers and potential therapeutic targets for beta-thalassemia.