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10.1021/acschembio.8b00454 http://scihub22266oqcxt.onion/10.1021/acschembio.8b00454 29893552/?report=reader!6126901!29893552     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29893552&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       ACS+Chem+Biol 2018 ; 13 (8): 2288-2299 Nephropedia Template TP {{tp|p=29893552|t=2018. Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD |pdf=|usr=}}{{29893552}} gab.com Text Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD JO: ACS Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=29893552 #FOAvip Genetic and epigenetic alterations in FK506-binding protein 5 ( FKBP5) have been associated with increased risk for psychiatric disorders, including post-traumatic stress disorder (PTSD). Some of these common variants can increase the expression of FKBP5, the gene that encodes FKBP51. Excess FKBP51 promotes hypothalamic-pituitary-adrenal (HPA) axis dysregulation through altered glucocorticoid receptor (GR) signaling. Thus, we hypothesized that GR activity could be restored by perturbing FKBP51. Here, we screened 1280 pharmacologically active compounds and identified three compounds that rescued FKBP51-mediated suppression of GR activity without directly activating GR. One of the three compounds, benztropine mesylate, disrupted the association of FKBP51 with the GR/Hsp90 complex in vitro. Moreover, we show that removal of FKBP51 from this complex by benztropine restored GR localization in ex vivo brain slices and primary neurons from mice. In conclusion, we have identified a novel disruptor of the FKBP51/GR/Hsp90 complex. Targeting this complex may be a viable approach to developing treatments for disorders related to aberrant FKBP51 expression. Twit Text FOAVip Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD ????ACS Chem Biol http://www.kidney.de/pget.php?&tw=1&pmid=29893552 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29893552 #FOAvip English Wikipedia <ref>{{Cite pmid|29893552}}</ref> Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD #MMPMID29893552 Sabbagh JJ; Cordova RA; Zheng D; Criado-Marrero M; Lemus A; Li P; Baker JD; Nordhues BA; Darling AL; Martinez-Licha C; Rutz DA; Patel S; Buchner J; Leahy JW; Koren J 3rd; Dickey CA; Blair LJ ACS Chem Biol 2018[Aug]; 13 (8): 2288-2299 PMID29893552show ga Genetic and epigenetic alterations in FK506-binding protein 5 ( FKBP5) have been associated with increased risk for psychiatric disorders, including post-traumatic stress disorder (PTSD). Some of these common variants can increase the expression of FKBP5, the gene that encodes FKBP51. Excess FKBP51 promotes hypothalamic-pituitary-adrenal (HPA) axis dysregulation through altered glucocorticoid receptor (GR) signaling. Thus, we hypothesized that GR activity could be restored by perturbing FKBP51. Here, we screened 1280 pharmacologically active compounds and identified three compounds that rescued FKBP51-mediated suppression of GR activity without directly activating GR. One of the three compounds, benztropine mesylate, disrupted the association of FKBP51 with the GR/Hsp90 complex in vitro. Moreover, we show that removal of FKBP51 from this complex by benztropine restored GR localization in ex vivo brain slices and primary neurons from mice. In conclusion, we have identified a novel disruptor of the FKBP51/GR/Hsp90 complex. Targeting this complex may be a viable approach to developing treatments for disorders related to aberrant FKBP51 expression. |Animals[MESH] |Benztropine/chemistry/*pharmacology[MESH] |Brain/drug effects/metabolism[MESH] |Cells, Cultured[MESH] |Depression/*drug therapy/metabolism[MESH] |Drug Discovery[MESH] |HSP90 Heat-Shock Proteins/*metabolism[MESH] |Humans[MESH] |Mice[MESH] |Molecular Targeted Therapy[MESH] |Protein Binding/drug effects[MESH] |Receptors, Glucocorticoid/*metabolism[MESH] |Stress Disorders, Post-Traumatic/*drug therapy/metabolism[MESH]Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevan(epmc).pdf DeepDyve Pubget Overpricing