转运蛋白
神经活性类固醇
别孕甾酮
抗焦虑药
神经科学
γ-氨基丁酸受体
变构调节
神经炎症
抗抑郁药
药理学
精神病
心理学
受体
医学
内科学
精神科
炎症
海马体
作者
Rainer Rupprecht,Christian H. Wetzel,Mario M. Dorostkar,Jochen Herms,Nathalie L. Albert,Jens Schwarzbach,Michaël Schumacher,Inga D. Neumann
标识
DOI:10.1038/s41380-022-01561-3
摘要
Efficient treatment of stress-related disorders, such as depression, is still a major challenge. The onset of antidepressant drug action is generally quite slow, while the anxiolytic action of benzodiazepines is considerably faster. However, their long-term use is impaired by tolerance development, abuse liability and cognitive impairment. Benzodiazepines act as positive allosteric modulators of ɣ-aminobutyric acid type A (GABAA) receptors. 3α-reduced neurosteroids such as allopregnanolone also are positive allosteric GABAA receptor modulators, however, through a site different from that targeted by benzodiazepines. Recently, the administration of neurosteroids such as brexanolone or zuranolone has been shown to rapidly ameliorate symptoms in post-partum depression or major depressive disorder. An attractive alternative to the administration of exogenous neurosteroids is promoting endogenous neurosteroidogenesis via the translocator protein 18k Da (TSPO). TSPO is a transmembrane protein located primarily in mitochondria, which mediates numerous biological functions, e.g., steroidogenesis and mitochondrial bioenergetics. TSPO ligands have been used in positron emission tomography (PET) studies as putative markers of microglia activation and neuroinflammation in stress-related disorders. Moreover, TSPO ligands have been shown to modulate neuroplasticity and to elicit antidepressant and anxiolytic therapeutic effects in animals and humans. As such, TSPO may open new avenues for understanding the pathophysiology of stress-related disorders and for the development of novel treatment options.
科研通智能强力驱动
Strongly Powered by AbleSci AI