Peptide neurotransmitters and peptide hormones, collectively known as neuropeptides, are required for cell-cell communication in neurotransmission and for regulation of endocrine functions. Neuropeptides are synthesized from protein precursors (termed proneuropeptides or prohormones) that require proteolytic processing primarily within secretory vesicles that store and secrete the mature neuropeptides to control target cellular and organ systems. This review describes interdisciplinary strategies that have elucidated two primary protease pathways for prohormone processing consisting of the cysteine protease pathway mediated by secretory vesicle cathepsin L and the well-known subtilisin-like proprotein convertase pathway that together support neuropeptide biosynthesis. Importantly, this review discusses important areas of current and future biomedical neuropeptide research with respect to biological regulation, inhibitors, structural features of proneuropeptide and protease interactions, and peptidomics combined with proteomics for systems biological approaches. Future studies that gain in-depth understanding of protease mechanisms for generating active neuropeptides will be instrumental for translational research to develop pharmacological strategies for regulation of neuropeptide functions. Pharmacological applications for neuropeptide research may provide valuable therapeutics in health and disease.

中文翻译：

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用于将原神经肽加工成肽神经递质和激素的蛋白酶。


肽类神经递质和肽类激素统称为神经肽，是神经传递中细胞间通讯和内分泌功能调节所必需的。神经肽由蛋白质前体（称为原神经肽或激素原）合成，主要需要在分泌囊泡内进行蛋白水解加工，分泌囊泡储存和分泌成熟的神经肽以控制靶细胞和器官系统。这篇综述描述了阐明激素原加工的两种主要蛋白酶途径的跨学科策略，包括由分泌囊泡组织蛋白酶 L 介导的半胱氨酸蛋白酶途径和众所周知的枯草杆菌蛋白酶样前蛋白转化酶途径，它们共同支持神经肽生物合成。重要的是，这篇综述讨论了当前和未来生物医学神经肽研究的重要领域，包括生物调节、抑制剂、原神经肽和蛋白酶相互作用的结构特征，以及肽组学与蛋白质组学相结合的系统生物学方法。未来深入了解产生活性神经肽的蛋白酶机制的研究将有助于转化研究开发调节神经肽功能的药理学策略。神经肽研究的药理学应用可能为健康和疾病提供有价值的治疗方法。