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Hemoglobin disorder by Mind Map: Hemoglobin disorder

1. Classification

1.1. Inherited

1.1.1. Qualitative Sickle cell disease (SCD) --- Glu to Val (hydrophobic) (HbS) --- At low oxygen --- polymerization --- malfunction to bind oxygen, generate superoxide, damage cytoskeleton, dehydration (K:Cl co-transporter) --- increase hemolysis HbC HbE

1.1.2. Quantitative : Thalassemia Alpha thalassemia Beta thalassemia

1.2. Acquired

1.2.1. MetHb (Fe2+ to Fe3+) --- unstable to bind oxygen --- hypoxia --- cyanosis

2. Treatment

2.1. fetal hemoglobin (HbF)

2.1.1. HbF inducers hydroxyurea Pharmocogenomics erythroid regeneration activate cGMP-dependent protein kinase erythropoietin erythroid regeneration cisplatin Most potent inducer high toxicity myleran Short chain fatty acids Combination of gene therapy natural compounds angelicin linear psoralens resveratrol rapamycin Mithramycin ethanol extracts Fructus trichosanthis Histone deacetylase (HDAC) inhibitor agents Sodium butylate butylate 5-azacitidine apicidin Trichostatin decitabine hydroxamic acid derivatives new immunomodulator drugs synergistic effect of drug efficient induction different mechanisms of each drug

2.1.2. Mechanism trigger several molecular signaling pathways (all signaling pathway are triggered by EPO) JAK/STAT MAPK(mitogen activated protein kinas) Phosphoinositide 3-kinase(PI3K) RAS Molecular targets (regulating erythroid transcription factor and erythroid gene expression programs) BCL11A SOX6 KLF1 c-MYb miRNAs 15a miRNA 16-1 HDAC1 HDAC2 Chromatin modifiers Histone deacetylase (HDAC) inhibitor agents DNA binding

2.1.3. during fetal life for transport oxygen

2.1.4. Advantage of increase HbF to prevent the beta-hemoglobinopathies beta-thalassemia HbE disease sickle cell Autosomal recessive inheritance treatment

2.1.5. target for study Chemical compound for induce HbF mechanism action of these drugs step for add drugs in Phase 2 genetic regulation of switch (HbA to HbF)

2.1.6. experiment in vivo mice baboon in vitro cell culture