Therapeutic Relevance of Inducing Autophagy in ß-Thalassemia.
Cells
; 13(11)2024 May 25.
Article
de En
| MEDLINE
| ID: mdl-38891049
ABSTRACT
The ß-thalassemias are inherited genetic disorders affecting the hematopoietic system. In ß-thalassemias, more than 350 mutations of the adult ß-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 α-globin. Possible experimental strategies for a reduction in excess free α-globin chains in ß-thalassemia are CRISPR-Cas9-based genome editing of the ß-globin gene, forcing "de novo" HbA production and fetal hemoglobin (HbF) induction. In addition, a reduction in excess free α-globin chains in ß-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 α-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 ß-thalassemia.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Autophagie
/
Bêta-Thalassémie
Limites:
Animals
/
Humans
Langue:
En
Journal:
Cells
Année:
2024
Type de document:
Article
Pays d'affiliation:
Italie
Pays de publication:
Suisse