PDF(Pubmed)
Abstract：
Stress-induced mental health disorders are affecting many people around the world. However, effective drug therapy for curing psychiatric diseases does not occur sufficiently. Many neurotransmitters, hormones, and mechanisms are essential in regulating the body\'s stress response. One of the most critical components of the stress response system is the hypothalamus-pituitary-adrenal (HPA) axis. The FKBP prolyl isomerase 51 (FKBP51) protein is one of the main negative regulators of the HPA axis. FKBP51 negatively regulates the cortisol effects (the end product of the HPA axis) by inhibiting the interaction between glucocorticoid receptors (GRs) and cortisol, causing reduced transcription of downstream cortisol molecules. By regulating cortisol effects, the FKBP51 protein can indirectly regulate the sensitivity of the HPA axis to stressors. Previous studies have indicated the influence of FKBP5 gene mutations and epigenetic changes in different psychiatric diseases and drug responses and recommended the FKBP51 protein as a drug target and a biomarker for psychological disorders. In this review, we attempted to discuss the effects of the FKBP5 gene, its mutations on different psychiatric diseases, and drugs affecting the FKBP5 gene.
摘要：
压力引起的心理健康障碍正在影响世界各地的许多人。然而,治疗精神疾病的有效药物治疗没有充分发生。许多神经递质，荷尔蒙，和机制在调节身体的应激反应中是必不可少的。应激反应系统的最关键组成部分之一是下丘脑-垂体-肾上腺（HPA）轴。FKBP原氨酰异构酶51(FKBP51)卵白是HPA轴的主要负调控因子之一。FKBP51通过抑制糖皮质激素受体（GR）和皮质醇之间的相互作用负调节皮质醇作用（HPA轴的最终产物），导致下游皮质醇分子转录减少。通过调节皮质醇效应，FKBP51蛋白可以间接调节HPA轴对应激源的敏感性。先前的研究表明FKBP5基因突变和表观遗传变化在不同精神疾病和药物反应中的影响，并推荐FKBP51蛋白作为药物靶标和心理障碍的生物标志物。在这次审查中,我们试图讨论FKBP5基因的作用，它在不同精神疾病上的突变，以及影响FKBP5基因的药物.
