Scholarlink

Objective <p>Neprilysin (NEP) is a multifunctional, therapeutically relevant, zinc-dependent membrane endopeptidase with significant implications for neurodegenerative, cardiovascular, renal, and metabolic pathophysiology, as well as cancer. While its broad substrate specificity (&gt; 30 peptides) and tissue-restricted expression have been extensively documented, integrated understanding of NEP’s disease-context-dependent functions and emerging therapeutic opportunities remains limited.</p> Methods <p>Recent literature was reviewed to summarize current findings on NEP structure, function, and dysregulation across diverse biological and disease contexts. Relevant studies were identified through searches of PubMed and Google Scholar.</p> Results <p>NEP exhibits remarkable functional plasticity, executing either protective or pathogenic roles depending on its substrate spectrum within specific disease contexts. In the central nervous system, NEP predominantly exerts neuroprotective functions by degrading toxic amyloid peptides, where its age-related decline and/or oxidative dysfunction critically contribute to Alzheimer’s disease. In the cardiovascular and renal systems, NEP-mediated processing of natriuretic peptides necessitates therapeutic inhibition to preserve their cardio-renoprotective effects, as demonstrated by the clinical success of sacubitril/valsartan in heart failure. In oncology, NEP primarily functions as a tumor suppressor with its epigenetic silencing correlating with cancer progression.</p> Conclusion <p>NEP represents a paradigmatic example of enzyme biology, where identical catalytic activity can lead to divergent clinical outcomes. Because NEP exerts both beneficial and pathogenic effects, indiscriminate systemic inhibition or activation is potentially challenging; targeted, tissue-specific modulation is thus required to minimize off-target consequences. Advanced delivery technologies and a deeper mechanistic understanding of NEP regulation have now created unprecedented opportunities to develop substrate‑specific or tissue‑targeted NEP modulators for multiple therapeutic indications.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Neprilysin, a Multifunctional Peptidase: Molecular Functions and Roles in Human Disease

  • 期刊论文

  • 发表日期：

    2026年3月26日

查看全文
  • Javad Gharechahi

摘要

Objective

Neprilysin (NEP) is a multifunctional, therapeutically relevant, zinc-dependent membrane endopeptidase with significant implications for neurodegenerative, cardiovascular, renal, and metabolic pathophysiology, as well as cancer. While its broad substrate specificity (> 30 peptides) and tissue-restricted expression have been extensively documented, integrated understanding of NEP’s disease-context-dependent functions and emerging therapeutic opportunities remains limited.

Methods

Recent literature was reviewed to summarize current findings on NEP structure, function, and dysregulation across diverse biological and disease contexts. Relevant studies were identified through searches of PubMed and Google Scholar.

Results

NEP exhibits remarkable functional plasticity, executing either protective or pathogenic roles depending on its substrate spectrum within specific disease contexts. In the central nervous system, NEP predominantly exerts neuroprotective functions by degrading toxic amyloid peptides, where its age-related decline and/or oxidative dysfunction critically contribute to Alzheimer’s disease. In the cardiovascular and renal systems, NEP-mediated processing of natriuretic peptides necessitates therapeutic inhibition to preserve their cardio-renoprotective effects, as demonstrated by the clinical success of sacubitril/valsartan in heart failure. In oncology, NEP primarily functions as a tumor suppressor with its epigenetic silencing correlating with cancer progression.

Conclusion

NEP represents a paradigmatic example of enzyme biology, where identical catalytic activity can lead to divergent clinical outcomes. Because NEP exerts both beneficial and pathogenic effects, indiscriminate systemic inhibition or activation is potentially challenging; targeted, tissue-specific modulation is thus required to minimize off-target consequences. Advanced delivery technologies and a deeper mechanistic understanding of NEP regulation have now created unprecedented opportunities to develop substrate‑specific or tissue‑targeted NEP modulators for multiple therapeutic indications.