Neuropeptidomics Mass Spectrometry Reveals Signaling Networks Generated by Distinct Protease Pathways in Human Systems
Neuropeptidomics Mass Spectrometry Reveals Signaling Networks Generated by Distinct Protease Pathways in Human Systems
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DOI：
10.1007/s13361-015-1251-6
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发表时间：
2015-12-01
影响因子：
3.2
通讯作者：
Bandeira, Nuno
中科院分区：
文献类型：
--
作者：
Hook, Vivian;Bandeira, Nuno
神经肽作为中枢和外周神经系统的神经递质以及作为内分泌系统中的肽激素调节细胞间信号传导。不同长度的不同一级序列的不同神经肽，通常具有翻译后修饰，协调和整合生理功能的调节。在神经肽组学研究中，基于质谱的不同神经肽结构的分析对于确定完整的神经肽信号分子是必要的。人类神经肽组学在定义人类健康和疾病中正常和功能失调的神经肽信号传导方面具有显着的重要性。神经肽组学在定义人类疾病的神经肽机制、为药物发现提供新的神经肽药物靶点以及监测神经肽作为药物反应的生物标志物方面具有巨大的扩展潜力。考虑到人类神经肽组学对健康的高度影响，在该学科中观察到的差距是与例如人类蛋白质组学和相关质谱学学科相比，人类神经肽组学中发表的文章很少。对人类神经肽组学的关注将促进对参与神经内分泌系统精细控制的复杂神经肽信号网络的新认识。这篇评论文章讨论了几个人类神经肽组学的成就，说明了迅速扩大的神经肽的多样性所产生的蛋白酶加工的前神经肽前体发生在分泌囊泡蛋白质组。特别令人感兴趣的是发现人特异性组织蛋白酶V参与产生脑啡肽和可能的其他神经肽，表明产生人神经肽的独特蛋白水解机制。人类神经肽组学领域在解决疾病状况中的新机制方面具有很大的前景，从而产生用于人类疾病的新药物靶标和治疗剂。
Neuropeptides regulate intercellular signaling as neurotransmitters of the central and peripheral nervous systems, and as peptide hormones in the endocrine system. Diverse neuropeptides of distinct primary sequences of various lengths, often with post-translational modifications, coordinate and integrate regulation of physiological functions. Mass spectrometry-based analysis of the diverse neuropeptide structures in neuropeptidomics research is necessary to define the full complement of neuropeptide signaling molecules. Human neuropeptidomics has notable importance in defining normal and dysfunctional neuropeptide signaling in human health and disease. Neuropeptidomics has great potential for expansion in translational research opportunities for defining neuropeptide mechanisms of human diseases, providing novel neuropeptide drug targets for drug discovery, and monitoring neuropeptides as biomarkers of drug responses. In consideration of the high impact of human neuropeptidomics for health, an observed gap in this discipline is the few published articles in human neuropeptidomics compared with, for example, human proteomics and related mass spectrometry disciplines. Focus on human neuropeptidomics will advance new knowledge of the complex neuropeptide signaling networks participating in the fine control of neuroendocrine systems. This commentary review article discusses several human neuropeptidomics accomplishments that illustrate the rapidly expanding diversity of neuropeptides generated by protease processing of pro-neuropeptide precursors occurring within the secretory vesicle proteome. Of particular interest is the finding that human-specific cathepsin V participates in producing enkephalin and likely other neuropeptides, indicating unique proteolytic mechanisms for generating human neuropeptides. The field of human neuropeptidomics has great promise to solve new mechanisms in disease conditions, leading to new drug targets and therapeutic agents for human diseases.