MME

MME Full Name

membrane metallo-endopeptidase

MME Introduction

MME, also known as membrane metallo-endopeptidase or neprilysin, represents a zinc-dependent cell-surface protease encoded by the MME gene. Rather than acting as a typical intracellular enzyme, MME resides predominantly on the plasma membrane of diverse cell types—including renal tubular epithelium, vascular endothelium, and specific neuronal populations—where its catalytic domain faces the extracellular milieu. It was originally characterized by its ability to cleave small peptides at neutral pH and has since been recognized as one of the principal peptidases capable of degrading a wide array of physiologically active peptides. The structural requirements for zinc coordination and peptide processing place MME within the broader M13 family of metalloproteases, and its gene expression is tightly regulated across tissues and during development.

Figure 1. Molecular Structure and Plasma Membrane Localization of MME (Neprilysin).

What distinguishes MME functionally is its broad peptide substrate repertoire and its role as a dynamic modulator of peptide signaling in diverse physiological contexts. MME can cleave bioactive peptides such as natriuretic peptides, bradykinin, substance P, endorphins, and amyloid-β, thereby attenuating or terminating their signaling. This substrate diversity allows MME to influence cardiovascular homeostasis by metabolizing natriuretic peptides that regulate blood pressure and volume, modulate nociceptive circuits through neuropeptide turnover, and participate in neuropeptide clearance within the central nervous system. Because MME does not simply inactivate peptides but reshapes peptide gradients and receptor engagement, its activity acts as a rheostat tuning multiple physiological networks rather than a binary on/off switch.

Dysregulation of MME activity has emerged as a biologically significant factor in several disease processes. In the cardiovascular arena, altered MME expression or inhibition influences levels of vasoactive peptides and underpins therapeutic strategies in heart failure, where neprilysin inhibitors combined with renin-angiotensin system blockers have demonstrated clinical benefit by preserving natriuretic peptide signaling. In the nervous system, MME's ability to degrade amyloid-β peptides has linked it to Alzheimer's disease pathogenesis, where reduced neprilysin activity may contribute to amyloid accumulation and neurodegeneration. Aberrant expression of MME has also been observed in various cancers, impacting tumor microenvironment peptide dynamics and offering a potential biomarker or target in oncology research. These multifaceted roles drive demand for research reagents such as MME antibodies, activity assays, recombinant proteins, and inhibitor screening tools, which are employed to dissect neprilysin's contributions to normal physiology and pathological remodeling in experimental systems and translational investigations.

Alternate Names for MME

MME; membrane metallo-endopeptidase; NEP; SFE; CD10; CALLA; neprilysin; enkephalinase; atriopeptidase; neprilysin-390

• 1. Cervellini I, et al.; Membrane metallo-endopeptidase is dispensable for repair after nerve injury. Glia. 2019, 67(10):1990-2000.