The corticotropin-releasing factor (CRF) family of neuropeptides in inflammation: Potential therapeutic applications
The corticotropin-releasing factor (CRF) family of neuropeptides in inflammation: Potential therapeutic applications
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DOI：
10.2174/0929867054039008
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发表时间：
2005-01-01
影响因子：
4.1
通讯作者：
Margioris, AN
中科院分区：
文献类型：
--
作者：
Gravanis, A;Margioris, AN
下丘脑CRF在协调应激的内分泌和行为反应中起着重要作用，它还参与了包括抑郁症、焦虑症和成瘾在内的多种神经精神疾病的病理生理学。在哺乳动物中，CRF肽家族包括CRF、尿皮质素（Ucn）、Ucn 1和Ucn II，同时富含新成员尿皮质素。它们的生物学效应由属于G蛋白偶联受体超家族的CRF1和CRF2受体介导。在过去的十年中，多个研究小组已经证明了CRF肽及其受体在免疫系统的几种组分中的表达，以及它们参与炎症现象的特设调节。非肽类CRF1拮抗剂最近被合成用于治疗中枢神经系统相关疾病，如焦虑、抑郁和药物滥用。在胃肠道中，这些化合物在治疗与CRF相关的下GI炎性疾病（例如慢性炎性肠综合征、肠易激综合征和溃疡性结肠炎）中开辟了新的治疗选择，而Ucn、Ucn 1、Ucn 11或合成的非肽CRF 2激动剂可用于治疗上GI炎性疾病。在人子宫内膜中，CRF I拮抗剂可用作流产剂。干扰在孕体植入期间发生的炎症现象。因此，它们可能代表一类新的非甾体类着床抑制剂。这两个例子说明了CRH在调节炎症现象中的潜在治疗意义，而不影响免疫系统的其余部分。
Hypothalamic CRF plays a central role in the coordination of endocrine and behavioral responses to stress and it is also involved in the pathophysiology of several neuropsychiatric diseases including depression, anxiety and addiction. In the mammals, the CRF family of peptides includes CRF, urocortin (Ucn), Ucn 1, and Ucn II while was enriched with new members, the urocortins. Their biological effects are mediated by the CRF1 and CRF2 receptors, which belong to the G-protein-coupled receptor super family. Multiple research groups have demonstrated during the last decade the expression of the CRF peptides and their receptors in several components of the immune system and their participation in the ad hoc regulation of inflammatory phenomena. Non-peptide CRF1 antagonists have been recently synthesized for the treatment of CNS related diseases, such as anxiety, depression and drug abuse. In the gastrointestinal tract, these compounds open new therapeutic options in the treatment of lower-GI inflammatory diseases associated to CRF, such as the chronic inflammatory bowel syndromes, irritable bowel disease and ulcerative colitis while Ucn, Ucn 1, Ucn 11 or synthetic non-peptide CRF2 agonists may be useful in the treatment of upper-GI inflammatory diseases. In human endometrium, CRF I antagonists may be used as abortive agents. interfering with the inflammatory phenomena taking place during the implantation of the conceptus. They thus may represent a new class of nonsteroidal inhibitors of implantation. These two examples illustrate the potential therapeutic significance of the CRH in regulating inflammatory phenomena in an ad hoc approach without affecting the rest of the immune system.