Ramping up stress resilience through inhibition of the cochaperone FKBP51
作者单位：Max Planck Institute of Psychiatry Department Stress Neurobiology and Neurogenetics
会议名称：《中国神经科学学会第十二届全国学术会议》
会议日期：2017年
学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学]
摘 要：The increasing rate of stress-related disorders, with mood disorders as major depression leading the way, and the social and well as economic consequences of these illnesses represent a growing threat to our society. A dysregulation of the body’s main stress system, the hypothalamic-pituitary-adrenal axis, is a major hallmark of depression, but so far no specific treatments tackling this mechanism are available. The co-chaperone FK506-binding protein 51（FKBP51） is a very promising target molecule for new drug therapies, as it directly regulates stress hormone activity. In humans, polymorphisms in the FKBP5 gene have been repeatedly linked to major depression and posttraumatic stress disorder. To further explore the interaction of FKBP51 with stress-related disorders, we have utilized conditional FKBP51 knockout or overexpression in combination with chronic social defeat stress, and tested the animals on different endocrine and behavioral parameters. Our results demonstrate that lowering FKBP51 levels in specific brain areas improves stress resilience. Treatment with the recently developed specific antagonist for FKBP51, SAFit2, lowered anxiety, improved stresscoping behavior and ameliorated the effects of chronic social defeat stress. Taken together, our results now pave the way for tailored and specific treatment strategies that could be beneficial for improving stress resilience in health and disease.