Neprilysin (NEP) is an integral membrane-bound metallopeptidase with a wide spectrum of substrates and physiological functions. It plays an important role in proteolytic processes in the kidney, cardiovascular regulation, immune response, cell proliferation, foetal development etc. It is an important neuropeptidase and amyloid-degrading enzyme which makes NEP a therapeutic target in Alzheimer’s disease (AD). Moreover, it plays a preventive role in development of cancer, obesity and type-2 diabetes. Recently a role of NEP in COVID-19 pathogenesis has also been suggested. Despite intensive research into NEP structure and functions in different organisms, changes in its expression and regulation during brain development and ageing, especially in age-related pathologies, is still not fully understood. This prevents development of pharmacological treatments from various diseases in which NEP is implicated although recently a dual-acting drug sacubitril-valsartan (LCZ696) combining a NEP inhibitor and angiotensin receptor blocker has been approved for treatment of heart failure. Also, various natural compounds capable of upregulating NEP expression, including green tea (EGCG), have been proposed as a preventive medicine in prostate cancer and AD. This review summarizes the existing literature and our own research on the expression and activity of NEP in normal brain development, ageing and under pathological conditions.

Neprilysin（NEP）是一种完整的膜结合金属肽酶，具有广泛的底物和生理功能。它在肾脏的蛋白水解过程，心血管调节，免疫反应，细胞增殖，胎儿发育等过程中起着重要作用。它是重要的神经肽酶和淀粉样蛋白降解酶，使NEP成为阿尔茨海默病（AD）的治疗靶标。此外，它在癌症，肥胖症和2型糖尿病的发生中起到预防作用。最近还提出了NEP在COVID-19发病机理中的作用。尽管深入研究了NEP在不同生物体中的结构和功能，但在大脑发育和衰老期间，尤其是在与年龄相关的病理过程中，其表达和调控的变化仍未完全了解。尽管最近已经批准了一种结合了NEP抑制剂和血管紧张素受体阻滞剂的双效药物沙比特利-缬沙坦（LCZ696）用于治疗心力衰竭，但这阻止了涉及NEP的多种疾病的药物治疗。另外，已经提出了各种能够上调NEP表达的天然化合物，包括绿茶（EGCG），作为前列腺癌和AD的预防药物。这篇综述总结了现有文献以及我们在正常脑发育，衰老和病理条件下对NEP的表达和活性的研究。另外，已经提出了各种能够上调NEP表达的天然化合物，包括绿茶（EGCG），作为前列腺癌和AD的预防药物。这篇综述总结了现有文献以及我们在正常脑发育，衰老和病理条件下对NEP的表达和活性的研究。另外，已经提出了各种能够上调NEP表达的天然化合物，包括绿茶（EGCG），作为前列腺癌和AD的预防药物。这篇综述总结了现有文献以及我们在正常脑发育，衰老和病理条件下对NEP的表达和活性的研究。