title: The prospect of FKBP51 as a drug target.
abstract: The FK506 binding protein 51 (FKBP51) is best known as an Hsp90-associated co-chaperone that regulates the responsiveness of steroid hormone receptors. In human genetic association studies, FKBP51 has repeatedly been associated with emotion processing and numerous stress-related affective disorders. It has also been implicated in contributing to the glucocorticoid hyposensitivity observed in New World primates. More recently, several research groups have consistently shown a protective effect of FKBP51 knockout or knockdown on stress endocrinology and stress-coping behavior in animal models of depression and anxiety. The principal druggability of FKBP51 is exemplified by the prototypic FKBP ligands FK506 and rapamycin. Moreover, FKBP51 is highly suited for X-ray co-crystallography, which should facilitate the rational drug design of improved FKBP51 ligands. In summary, FKBP51 has emerged as a promising new drug target for stress-related disorders that should be amenable to drug discovery.
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich (Germany).
authors.forename: Mathias V
authors.initials: MV
authors.lastname: Schmidt
authors.forename: Marcelo
authors.initials: M
authors.lastname: Paez-Pereda
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Felix
authors.initials: F
authors.lastname: Hausch
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D015195:Drug Design; D004734:Energy Metabolism; D055785:Gene Knockdown Techniques; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D011987:Receptors, Steroid / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
chemical_list: D000928:Antidepressive Agents; D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D011987:Receptors, Steroid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5