A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51.
A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51.
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DOI：
10.1371/journal.pone.0024840
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Dickey CA
中科院分区：
文献类型：
--
作者：
O'Leary JC 3rd;Dharia S;Blair LJ;Brady S;Johnson AG;Peters M;Cheung-Flynn J;Cox MB;de Erausquin G;Weeber EJ;Jinwal UK;Dickey CA
FKBP 5基因编码FKBP 51，FKBP 51是Hsp 90复合物的共伴侣蛋白，随年龄增长而增加。通过与Hsp 90的结合，FKBP 51调节糖皮质激素受体（GR）。FKBP 5基因的单核苷酸多态性（SNPs）与HIV患者抑郁发作复发率增加、创伤后应激障碍、双相情感障碍、自杀未遂和重度抑郁症易感性增加相关。这些SNP之一的变异与FKBP 51水平的增加相关。FKBP 51在HIV患者中也增加。此外，杏仁核中FKBP 51的增加在小鼠中产生焦虑表型。因此，我们测试了老年小鼠中FKBP 5缺失的行为后果。与接受经典抗抑郁药治疗的未处理动物相似，FKBP 5 −/−小鼠表现出抗抑郁行为，而不影响认知和其他基本运动功能。压力后皮质酮水平降低伴随着这些观察到的对抑郁症的影响。FKBP 5缺失也可调节神经依赖性焦虑。因此，专注于消耗FKBP 51水平的药物发现工作可能会产生新的抗抑郁疗法。
The gene FKBP5 codes for FKBP51, a co-chaperone protein of the Hsp90 complex that increases with age. Through its association with Hsp90, FKBP51 regulates the glucocorticoid receptor (GR). Single nucleotide polymorphisms (SNPs) in the FKBP5 gene associate with increased recurrence of depressive episodes, increased susceptibility to post-traumatic stress disorder, bipolar disorder, attempt of suicide, and major depressive disorder in HIV patients. Variation in one of these SNPs correlates with increased levels of FKBP51. FKBP51 is also increased in HIV patients. Moreover, increases in FKBP51 in the amygdala produce an anxiety phenotype in mice. Therefore, we tested the behavioral consequences of FKBP5 deletion in aged mice. Similar to that of naïve animals treated with classical antidepressants FKBP5−/− mice showed antidepressant behavior without affecting cognition and other basic motor functions. Reduced corticosterone levels following stress accompanied these observed effects on depression. Age-dependent anxiety was also modulated by FKBP5 deletion. Therefore, drug discovery efforts focused on depleting FKBP51 levels may yield novel antidepressant therapies.
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影响因子：
11
作者：
Willour, V. L.;Chen, H.;Potash, J. B.
通讯作者：
Potash, J. B.
影响因子：
3.7
作者：
Binder, E. B.;Kuenzel, H. E.;Holsboer, F.
通讯作者：
Holsboer, F.
影响因子：
30.8
作者：
Binder, EB;Salyakina, D;Muller-Myhsok, B
通讯作者：
Muller-Myhsok, B
DOI：
10.1038/npp.2010.37
发表时间：
2010-07
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
STERU, L;CHERMAT, R;SIMON, P
通讯作者：
SIMON, P