title: Small molecules targeting glycogen synthase kinase 3 as potential drug candidates for the treatment of retinitis pigmentosa.
abstract: Retinitis pigmentosa (RP) is an inherited retinal dystrophy that courses with progressive degeneration of retinal tissue and loss of vision. Currently, RP is an unpreventable, incurable condition. We propose glycogen synthase kinase 3 (GSK-3) inhibitors as potential leads for retinal cell neuroprotection, since the retina is also a part of the central nervous system and GSK-3 inhibitors are potent neuroprotectant agents. Using a chemical genetic approach, diverse small molecules with different potency and binding mode to GSK-3 have been used to validate and confirm GSK-3 as a pharmacological target for RP. Moreover, this medicinal chemistry approach has provided new leads for the future disease-modifying treatment of RP.
authors.affiliation: a Department of Cellular and Molecular Medicine , Centro de Investigaciones Biológicas (CSIC) , Madrid , Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Marchena
authors.affiliation: a Department of Cellular and Molecular Medicine , Centro de Investigaciones Biológicas (CSIC) , Madrid , Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Villarejo-Zori
authors.affiliation: b Department of Chemical and Physical Biology , Centro de Investigaciones Biológicas (CSIC) , Madrid , Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: Zaldivar-Diez
authors.affiliation: b Department of Chemical and Physical Biology , Centro de Investigaciones Biológicas (CSIC) , Madrid , Spain.
authors.forename: Valle
authors.initials: V
authors.lastname: Palomo
authors.affiliation: b Department of Chemical and Physical Biology , Centro de Investigaciones Biológicas (CSIC) , Madrid , Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gil
authors.affiliation: a Department of Cellular and Molecular Medicine , Centro de Investigaciones Biológicas (CSIC) , Madrid , Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: Hernández-Sánchez
authors.affiliation: b Department of Chemical and Physical Biology , Centro de Investigaciones Biológicas (CSIC) , Madrid , Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez
authors.affiliation: a Department of Cellular and Molecular Medicine , Centro de Investigaciones Biológicas (CSIC) , Madrid , Spain.
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: de la Rosa
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D038362:Glycogen Synthase Kinase 3
keywords: GSK-3 inhibitors; glaucoma; retinal diseases; retinitis pigmentosa