The FKBP51-Glucocorticoid Receptor Balance in Stress-Related Mental Disorders

被引:35
作者
Fries, Gabriel R. [1 ,2 ]
Gassen, Nils C. [1 ]
Schmidt, Ulrike [3 ]
Rein, Theo [1 ]
机构
[1] Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany
[2] Univ Texas Hlth Sci Ctr Houston UTHlth, Sch Med, Dept Psychiat & Behav Sci, Translat Psychiat Program, Houston, TX USA
[3] Max Planck Inst Psychiat, RG Mol Psychotraumatol, Dept Clin Res, Munich, Germany
关键词
FKBP51; glucocorticoid receptor; HPA axis; mental disorders; stress; HEAT-SHOCK-PROTEIN; GENE-ENVIRONMENT INTERACTIONS; FKBP5 VARIANT RS1360780; PITUITARY-ADRENAL AXIS; GLUCOCORTICOID-RECEPTOR; FK506-BINDING PROTEIN; ANDROGEN RECEPTOR; SQUIRREL-MONKEY; IMMUNOPHILIN FKBP52; TREATMENT RESPONSE;
D O I
10.2174/1874467208666150519114435
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The immunophilin FK506 binding protein 51 (FKBP51) has emerged as one of the most intensely investigated proteins in stress-related mental disorders. It was originally characterized as Hsp90 cochaperone and part of the receptor-chaperone heterocomplex that governs the activity of steroid receptors. It turned out that the presence of FKBP51 in this heterocomplex leads to diminished activity of the corticosteroid receptors. In particular, based on its inhibitory action on the glucocorticoid receptor (GR), FKBP51 was included in a candidate gene approach to discover gene polymorphisms that might be relevant for the development and treatment of major depression. The discovery that polymorphisms in the gene coding for FKBP51 were linked to the treatment response of depressed patients intensified the research on the role of FKBP51 in stress-related diseases worldwide. It has become evident that FKBP51 is not only a regulator of GR action, but also a GR target. The function of this ultrashort intracellular feedback loop is critically important for cellular and physiological stress regulation as it does not only calibrate the function of GR, but also the levels of FKBP51. Given the pleiotropic functions of FKBP51, its levels might be equally important for mental disorders as GR function and hence for the development of potential FKBP51 drug targets.
引用
收藏
页码:126 / 140
页数:15
相关论文
共 188 条
[1]   Role of environmental confounding in the association between FKBP5 and first-episode psychosis [J].
Ajnakina, Olesya ;
Borges, Susana ;
Di Forti, Marta ;
Patel, Yogen ;
Xu, Xiaohui ;
Green, Priscilla ;
Stilo, Simona A. ;
Kolliakou, Anna ;
Sood, Poonam ;
Marques, Tiago Reis ;
David, Anthony S. ;
Prata, Diana ;
Dazzan, Paola ;
Powell, John ;
Pariante, Carmine ;
Mondelli, Valeria ;
Morgan, Craig ;
Murray, Robin M. ;
Fisher, Helen L. ;
Iyegbe, Conrad .
FRONTIERS IN PSYCHIATRY, 2014, 5
[2]   Deficiency of FK506-binding protein ( FKBP) 51 alters sleep architecture and recovery sleep responses to stress in mice [J].
Albu, Stefana ;
Romanowski, Christoph P. N. ;
Curzi, M. Letizia ;
Jakubcakova, Vladimira ;
Flachskamm, Cornelia ;
Gassen, Nils C. ;
Hartmann, Jakob ;
Schmidt, Mathias V. ;
Schmidt, Ulrike ;
Rein, Theo ;
Holsboer, Florian ;
Hausch, Felix ;
Paez-Pereda, Marcelo ;
Kimura, Mayumi .
JOURNAL OF SLEEP RESEARCH, 2014, 23 (02) :176-185
[3]  
[Anonymous], INT J NEUROPSYCHOPHA
[4]   Moderation of Adult Depression by a Polymorphism in the FKBP5 Gene and Childhood Physical Abuse in the General Population [J].
Appel, Katja ;
Schwahn, Christian ;
Mahler, Jessie ;
Schulz, Andrea ;
Spitzer, Carsten ;
Fenske, Kristin ;
Stender, Jan ;
Barnow, Sven ;
John, Ulrich ;
Teumer, Alexander ;
Biffar, Reiner ;
Nauck, Matthias ;
Voelzke, Henry ;
Freyberger, Harald J. ;
Grabe, Hans J. .
NEUROPSYCHOPHARMACOLOGY, 2011, 36 (10) :1982-1991
[5]  
Arlt S, 2013, CURR ALZHEIMER RES, V10, P72
[6]   Neuropsin cleaves EphB2 in the amygdala to control anxiety [J].
Attwood, Benjamin K. ;
Bourgognon, Julie-Myrtille ;
Patel, Satyam ;
Mucha, Mariusz ;
Schiavon, Emanuele ;
Skrzypiec, Anna E. ;
Young, Kenneth W. ;
Shiosaka, Sadao ;
Korostynski, Michal ;
Piechota, Marcin ;
Przewlocki, Ryszard ;
Pawlak, Robert .
NATURE, 2011, 473 (7347) :372-U553
[7]   Rapamycin stimulates apoptosis of childhood acute lymphoblastic leukemia cells [J].
Avellino, R ;
Romano, S ;
Parasole, R ;
Bisogni, R ;
Lamberti, A ;
Poggi, V ;
Venuta, S ;
Romano, MF .
BLOOD, 2005, 106 (04) :1400-1406
[8]   Interplay between diet-induced obesity and chronic stress in mice: potential role of FKBP51 [J].
Balsevich, Georgia ;
Uribe, Andres ;
Wagner, Klaus V. ;
Hartmann, Jakob ;
Santarelli, Sara ;
Labermaier, Christiana ;
Schmidt, Mathias V. .
JOURNAL OF ENDOCRINOLOGY, 2014, 222 (01) :15-26
[9]   Analysis of FKBP51/FKBP52 chimeras and mutants for Hsp90 binding and association with progesterone receptor complexes [J].
Barent, RL ;
Nair, SC ;
Carr, DC ;
Ruan, Y ;
Rimerman, RA ;
Fulton, J ;
Zhang, Y ;
Smith, DF .
MOLECULAR ENDOCRINOLOGY, 1998, 12 (03) :342-354
[10]   Tissue distribution and abundance of human FKBP51, an FK506-binding protein that can mediate calcineurin inhibition [J].
Baughman, G ;
Wiederrecht, GJ ;
Chang, F ;
Martin, MM ;
Bourgeois, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 232 (02) :437-443