Neuropeptides are short peptides in the range of 3–40 residues that are secreted for cell-cell communication in neuroendocrine systems. In the nervous system, neuropeptides comprise the largest group of neurotransmitters. In the endocrine system, neuropeptides function as peptide hormones to coordinate intercellular signaling among target physiological systems. The diversity of neuropeptide functions is defined by their distinct primary sequences, peptide lengths, proteolytic processing of pro-neuropeptide precursors, and covalent modifications. Global, untargeted neuropeptidomics mass spectrometry is advantageous for defining the structural features of the thousands to tens of thousands of neuropeptides present in biological systems. Defining neuropeptide structures is the basis for defining the proteolytic processing pathways that convert pro-neuropeptides into active peptides. Neuropeptidomics has revealed that processing of pro-neuropeptides occurs at paired basic residues sites, and at non-basic residue sites. Processing results in neuropeptides with known functions and generates novel peptides representing intervening peptide domains flanked by dibasic residue processing sites, identified by neuropeptidomics. While very short peptide products of 2–4 residues are predicted from pro-neuropeptide dibasic processing sites, such peptides have not been readily identified; therefore, it will be logical to utilize metabolomics to identify very short peptides with neuropeptidomics in future studies. Proteolytic processing is accompanied by covalent post-translational modifications (PTMs) of neuropeptides comprising C-terminal amidation, N-terminal pyroglutamate, disulfide bonds, phosphorylation, sulfation, acetylation, glycosylation, and others. Neuropeptidomics can define PTM features of neuropeptides. In summary, neuropeptidomics for untargeted, global analyses of neuropeptides is essential for elucidation of proteases that generate diverse neuropeptides for cell-cell signaling.

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神经肽是在3-40个残基范围内的短肽，在神经内分泌系统中被分泌用于细胞间的通讯。在神经系统中，神经肽构成最大的一组神经递质。在内分泌系统中，神经肽起肽激素的作用，以协调靶生理系统之间的细胞间信号传导。神经肽功能的多样性由其独特的一级序列，肽长度，前神经肽前体的蛋白水解过程和共价修饰定义。全局非靶向神经肽组学质谱分析有利于确定生物系统中存在的数千至数万个神经肽的结构特征。定义神经肽结构是定义将前神经肽转化为活性肽的蛋白水解加工途径的基础。神经肽组学已揭示，前神经肽的加工发生在成对的碱性残基位点和非碱性残基位点。加工产生具有已知功能的神经肽，并产生代表中间肽结构域的新型肽，所述肽结构域侧接由神经肽组学鉴定的二元残基加工位点。虽然从前神经肽二元加工位点预测到有2–4个残基的非常短的肽产物，但尚不容易鉴定出这种肽。因此，在未来的研究中，利用代谢组学来鉴定具有神经肽组学的非常短的肽是合乎逻辑的。蛋白水解过程伴随着神经肽的共价翻译后修饰（PTM），包括C端酰胺化，N端焦谷氨酸，二硫键，磷酸化，硫酸化，乙酰化，糖基化等。神经肽组学可以定义神经肽的PTM特征。总而言之，对神经肽进行无针对性的全局分析的神经肽组学对于阐明产生细胞信号的多种神经肽的蛋白酶至关重要。

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