{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMME, also known as neutral endopeptidase (NEP) or CD10, is a zinc‐dependent cell‐surface metallopeptidase with broad substrate specificity. It catalyzes the proteolytic cleavage of diverse bioactive peptides—including components of the renin–angiotensin system, where it converts angiotensin I into angiotensin (1–7) with vasodilatory and homeostatic effects—and its detailed three‐dimensional structure reveals the essential requirement for zinc binding in substrate recognition and catalysis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the brain, MME/NEP plays a critical role in peptide homeostasis by degrading amyloid‐β peptides. Multiple studies have demonstrated that reduced NEP activity or expression correlates with increased levels of amyloid‐β and the formation of pathogenic plaques in Alzheimer’s disease. Gene transfer strategies and hormonal regulation (for example, via estrogen receptors) have been shown to up‐regulate NEP and promote amyloid‐β clearance in vivo, thereby offering therapeutic promise by decreasing amyloid burden."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMME also has important roles in renal and immunologic contexts. Aberrant expression or mutations in the MME gene have been implicated in immune‐mediated kidney disorders such as antenatal membranous glomerulonephritis, where NEP serves as a target antigen. Furthermore, in renal neoplasms the detection of CD10/NEP expression provides both prognostic and diagnostic value, and alterations in its levels have been linked to tumor aggressiveness in prostate and other cancers. In diabetic kidney disease, increased urinary NEP activity is thought to contribute to the local generation of protective peptides."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these roles, MME exerts significant influence on the extracellular microenvironment in various tissues. In the mammary gland, its enzymatic activity helps regulate stem cell function by cleaving local signaling peptides, while in the skin it degrades neuropeptides such as substance P, thereby modulating inflammatory responses and wound healing. These multifaceted functions underscore the enzyme’s importance not only as a key mediator of physiological peptide catabolism but also as a valuable diagnostic and prognostic marker in several malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gillian I Rice, Daniel A Thomas, Peter J Grant, et al. 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