Peptide therapeutics for CNS indications
Peptide therapeutics for CNS indications
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DOI：
10.1016/j.bcp.2011.10.014
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发表时间：
2012-03-01
影响因子：
5.8
通讯作者：
McGonigle, Paul
中科院分区：
文献类型：
--
作者：
McGonigle, Paul
神经肽在中枢神经系统的正常功能中发挥着至关重要的作用，肽受体作为治疗多种中枢神经系统疾病的治疗靶点具有广阔的前景。一般来说，肽疗法的发展因肽缺乏类药特性而受到限制，这使得将它们转化为可销售的治疗分子非常困难。其中一些挑战包括体内稳定性差、溶解度差、与口服给药不相容、储存稳定性、制造成本。最近的技术进步克服了许多这些限制，并导致用于糖尿病、癌症和疼痛等广泛治疗适应症的肽的开发快速增长。本综述探讨了肽激动剂治疗主要中枢神经系统疾病（如精神分裂症、焦虑症、抑郁症和自闭症）的治疗潜力。已经积累的临床和临床前数据支持激动剂对中枢神经降压素、胆囊收缩素、神经肽 Y 和催产素受体的潜在用途。还描述了一些已开发的提高肽在体内稳定性和寿命并改善其递送的成功方法，并讨论了克服中枢神经系统治疗特有的主要挑战（血脑屏障渗透）的潜在策略。 (C) 2011 Elsevier Inc. 保留所有权利。
Neuropeptides play a crucial role in the normal function of the central nervous system and peptide receptors hold great promise as therapeutic targets for the treatment of several CNS disorders. In general, the development of peptide therapeutics has been limited by the lack of drug-like properties of peptides and this has made it very difficult to transform them into marketable therapeutic molecules. Some of these challenges include poor in vivo stability, poor solubility, incompatibility with oral administration, shelf stability, cost of manufacture. Recent technical advances have overcome many of these limitations and have led to rapid growth in the development of peptides for a wide range of therapeutic indications such as diabetes, cancer and pain. This review examines the therapeutic potential of peptide agonists for the treatment of major CNS disorders such as schizophrenia, anxiety, depression and autism. Both clinical and preclinical data has been accumulated supporting the potential utility of agonists at central neurotensin, cholecystokinin, neuropeptide Y and oxytocin receptors. Some of the successful approaches that have been developed to increase the stability and longevity of peptides in vivo and improve their delivery are also described and potential strategies for overcoming the major challenge that is unique to CNS therapeutics, penetration of the blood-brain barrier, are discussed. (C) 2011 Elsevier Inc. All rights reserved.