The CRF System as a Therapeutic Target for Neuropsychiatric Disorders.
The CRF System as a Therapeutic Target for Neuropsychiatric Disorders.
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DOI：
10.1016/j.tips.2016.09.004
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发表时间：
2016-12
影响因子：
13.8
通讯作者：
Nemeroff C
中科院分区：
文献类型：
--
作者：
Sanders J;Nemeroff C
主要的神经精神疾病是对治疗只有适度反应的破坏性疾病。改善这些疾病的治疗将需要创新的新策略，这些策略将偏离以前专注于药理学机制。相当多的临床前和临床数据指出促肾上腺皮质激素释放因子（CRF）信号转导作为新的精神药物开发的目标。在这里，我们审查的CRF系统的变化报告在几个精神疾病。我们还研究了临床前工作，解剖了CRF受体在与这些疾病相关的特定回路中的独特作用。我们进一步描述了已进行的CRF1受体拮抗剂的临床试验。尽管这些临床试验迄今为止取得了有限的治疗成功，但CRF系统的复杂性为研究其在神经精神疾病的病因学和治疗中的作用提供了许多未来的方向。
The major neuropsychiatric disorders are devastating illnesses that are only modestly responsive to treatment. Improving the treatment of these conditions will require innovative new strategies that depart from previously focused upon pharmacological mechanisms. Considerable preclinical and clinical data point to Corticotropin-Releasing Factor (CRF) signaling as a target for new psychotropic drug development. Here we review alterations in the CRF system reported in several psychiatric conditions. We also examine the preclinical work that has dissected the distinctive roles for CRF receptors in specific circuits relevant to these disorders. We further describe the clinical trials of CRF1 receptor antagonists that have been conducted. Although these clinical trials have thus far met with limited therapeutic success, the unfolding complexity of the CRF system promises many future directions for studying its role in the etiology and treatment of neuropsychiatric conditions.