title: KDM1 histone lysine demethylases as targets for treatments of oncological and neurodegenerative disease.
abstract: Histone methylation and demethylation are important processes associated with the regulation of gene transcription, and alterations in histone methylation status have been linked to a large number of human diseases. Initially thought to be an irreversible process, histone methylation is now known to be reversed by two families of proteins containing over 30 members that act to remove methyl groups from specific lysine residues present in the tails of histone H3 and histone H4. A rapidly growing number of reports have implicated the FAD-dependent lysine specific demethylase (KDM1) family in cancer, and several small-molecule inhibitors are in development for the treatment of cancer. An additional role has emerged for KDM1 in brain function, offering additional opportunities for the development of novel therapeutic strategies in neurodegenerative disease. A decade after the identification of KDM1A as a histone demethylase, the first selective inhibitors have now reached the clinic.
authors.affiliation: Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornella de Llobregat, Barcelona, España.
authors.forename: Tamara
authors.initials: T
authors.lastname: Maes
authors.affiliation: Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornella de Llobregat, Barcelona, España.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mascaró
authors.affiliation: Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornella de Llobregat, Barcelona, España.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornella de Llobregat, Barcelona, España.
authors.forename: Serena
authors.initials: S
authors.lastname: Lunardi
authors.affiliation: Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornella de Llobregat, Barcelona, España.
authors.forename: Filippo
authors.initials: F
authors.lastname: Ciceri
authors.affiliation: Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, Manchester, M20 4BX, UK.
authors.forename: Tim C P
authors.initials: TC
authors.lastname: Somervaille
authors.affiliation: Oryzon Genomics S.A., Carrer Sant Ferran 74, 08940 Cornella de Llobregat, Barcelona, España.
authors.forename: Carlos
authors.initials: C
authors.lastname: Buesa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D044127:Epigenesis, Genetic; D015316:Genetic Therapy; D056466:Histone Demethylases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000628:therapy
chemical_list: D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: Alzheimer's disease; GSK2879552; Huntington's disease; ORY-1001; ORY-2001; SCLC; acute myeloid leukemia; histone lysine demethylases (KDMs); oncology