title: Lysine-specific demethylase 1 is a therapeutic target for fetal hemoglobin induction.
abstract: Enhanced fetal γ-globin synthesis alleviates symptoms of β-globinopathies such as sickle cell disease and β-thalassemia, but current γ-globin-inducing drugs offer limited beneficial effects. We show here that lysine-specific demethylase 1 (LSD1) inhibition by RNAi in human erythroid cells or by the monoamine oxidase inhibitor tranylcypromine in human erythroid cells or β-type globin-transgenic mice enhances γ-globin expression. LSD1 is thus a promising therapeutic target for γ-globin induction, and tranylcypromine may serve as a lead compound for the development of a new γ-globin inducer.
authors: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors: Lihong
authors: L
authors: Shi
authors: Shuaiying
authors: S
authors: Cui
authors: James D
authors: JD
authors: Engel
authors: Osamu
authors: O
authors: Tanabe
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics / Q000628:therapy; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000187:drug effects / Q000378:metabolism; D005319:Fetal Hemoglobin / Q000096:biosynthesis*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D011987:Receptors, Steroid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D014191:Tranylcypromine / Q000494:pharmacology*; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000235:genetics / Q000628:therapy; D055545:gamma-Globins / Q000096:biosynthesis
chemical_list: D008996:Monoamine Oxidase Inhibitors; C490515:NR2C2 protein, human; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D034741:RNA, Small Interfering; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D055544:beta-Globins; D055545:gamma-Globins; D014191:Tranylcypromine; D005319:Fetal Hemoglobin; D056466:Histone Demethylases; C495195:KDM1A protein, human