Role of intracellulare endothelin-converting enzyme-1 (ECE-1) as a regulator of neuropeptide function and signalling in the skin

细胞内内皮素转换酶 1 (ECE-1) 作为皮肤神经肽功能和信号传导调节剂的作用

• 批准号: 14188445
• 负责人: Professor Dr. Martin Steinhoff
• 金额: --
• 依托单位: UCD Charles Institute of Dermatology
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/14188445?language=en
• 关键词: Role; intracellulare; endothelin; converting; enzyme

Recent studies indicate that a variety of peptidases play an important part in the control of neurogenic inflammation. We have recently described a new mechanism showing that endothelinconverting enzyme-1 (ECE-1) cleaves and inactivates substance P in acidified endosomes, thereby freeing β-arrestins from the neurokinin 1 receptor (NK1R), which recycles to mediate receptor resensitization or signalling. Thus, peptidases such as ECE-1 may have important implications in the regulation of neurogenic inflammation and neuronal diseases by controlling neuropeptide receptor resensitization. This implicates that inhibitors of ECE-1 may be beneficial for the treatment of inflammation, pain and other neuronal/psychiatric disorders. The aim of this study will be to determine the precise mechanism of how ECE-1 regulates receptor resensitization in detail and investigates the role of ECE-1 in cutaneous inflammation.

最近的研究表明，多种肽酶在神经源性炎症的控制中起重要作用。我们最近描述了一种新的机制，表明内皮素转换酶-1（ECE-1）在酸化的核内体中切割并灭活P物质，从而从神经激肽1受体（NK 1 R）中释放β-arrestins，NK 1 R介导受体再敏化或信号传导。因此，肽酶，如ECE-1可能有重要的影响，在调节神经源性炎症和神经元疾病，通过控制神经肽受体再敏感。这意味着ECE-1抑制剂可能有益于治疗炎症、疼痛和其他神经元/精神疾病。本研究的目的是详细确定ECE-1如何调节受体再敏感的确切机制，并研究ECE-1在皮肤炎症中的作用。