Abstract
Sickle cell disease (SCD) is an autosomal recessive blood disorder which occurs due to point mutation in the β-globin chain of hemoglobin. Since the past decades, various therapies have been put forth, which are based on obstructing pathophysiological mechanisms of SCD including inhibition of Gardos channel and cation fluxes which in turn prevents sickle erythrocyte destruction and dehydration. The pharmacological approaches are based on the mechanism of reactivating γ-globin expression by utilizing fetal hemoglobin (HbF)-inducing drugs such as hydroxyurea. In SCD, gene therapy could be considered as a promising tool which involves modifying mutation at the gene-specific target by either promoting insertion or deletion of globins. Although there are various therapies emerged so far in the treatment of SCD, many of them have faced a major setback in most of developing countries in terms of cost, unavailability of expertise, and suitable donor. Therefore, in addition to pathophysiological aspects, this review will discuss new advancements and approaches made in the therapeutic domain of SCD including a viewpoint of modulating hemoglobin in SCD by the intervention of probiotics.
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Abbreviations
- SCD:
-
Sickle cell disease
- HbF:
-
Fetal hemoglobin
- HbS:
-
Sickle hemoglobin
- RBCs:
-
Red blood cells
- SCFAs:
-
Short-chain fatty acids
- VOC:
-
Vao-occlusive crisis
- NO:
-
Nitric oxide
- GM-CSF:
-
Granulocyte macrophage colony-stimulating factor
- G-CSF:
-
Granulocyte colony-stimulating factor
- NuRD:
-
Nucleosome remodeling deacetylase complex
- sGC:
-
Soluble guanylate cyclase
- MAPKs:
-
Mitogen-activated protein kinases
- ERK:
-
Extracellular signal-regulated protein kinase
- JNK:
-
c-Jun N-terminal kinase
- ROS:
-
Reactive oxygen species
- H2O2 :
-
Hydrogen peroxide
- elF2α:
-
Eukaryotic initiation factor 2α
- HDAC:
-
Histone deacetylase
- HDR:
-
Homology-directed repair
- cGMP:
-
Cyclic guanosine monophosphate pathway
- GCPRs:
-
G-coupled protein receptors
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We are thankful to Uka Tarsadia University, Bardoli, Gujarat, India, for providing necessary research facilities to conduct the study.
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FS and MD conceptualized the study and prepared the manuscript draft. MD reviewed, edited and submitted the manuscript.
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Shah, F., Dwivedi, M. Pathophysiology and recent therapeutic insights of sickle cell disease. Ann Hematol 99, 925–935 (2020). https://doi.org/10.1007/s00277-020-03977-9
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DOI: https://doi.org/10.1007/s00277-020-03977-9