What is Neprilysin?

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  • Written By: Misty Wiser
  • Edited By: Allegra J. Lingo
  • Last Modified Date: 13 November 2019
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Neprilysin is an enzyme that is also referred to as neutral endopeptidase (NEP). Some scientists prefer the term membrane metallo-endopeptidase to describe the attachment of the protein to the cell membrane. The enzyme neprilysin is sent from the Golgi apparatus within the cell body and secreted on the surface of the cell. It is produced by different organs within the body, including the brain, kidneys, and lungs. Lab tests may reveal low levels of this enzyme in persons with Alzheimer’s disease.

Getting older can decrease the production and activity levels of available extracellular NEP, and this may be a factor in the development of Alzheimer’s disease. People with Alzheimer’s disease lose the ability to remember events, places, names, and may even forget how to perform simple daily tasks. Eventually, some people may not be able to get dressed or eat without assistance. A person with an advanced stage of the disease may not be able to recognize his reflection in the mirror.

The activity of NEP can be increased by the presence of other peptide hormones. Production of the activity-inducing peptide compound called somatostatin also decreases as a person ages. Without the proper amount of somatostatin to excite the available NEP enzyme, the concentration of beta-amyloids in the extracellular fluid of the brain greatly increases. Additional plaque deposits are formed by the beta-amyloids, causing additional damage to the brain.


Studies of neprilysin gene transfer have shown encouraging results regarding the treatment of Alzheimer’s disease. The amount of the free-floating beta-amyloids responsible for damaging the brain is drastically decreased when neprilysin producing cells were injected into cerebral extracellular fluid. Neprilysin promotes the speedy degradation of beta-amyloid peptides, reducing the amount of plaque deposits formed within the brain.

The zinc metalloendopeptidase neprilysin may be identified on some test results as the common acute lymphoblastic leukemia antigen (CALLA). Some diseased lymphocytes produce additional amounts of this surface protein. Confirming an increase in the activity of CALLA may indicate the possibility of acute lymphocytic leukemia (ALL), follicular germinal center lymphoma, or Burkitt lymphoma.

Obese persons may have an increased NEP levels when tested. Adipose, or fat cells, produce more of the enzyme than can be used by the body. Metabolic disease or a high fat diet may result in additional neprilysin being stored in the fatty tissues. Increased neprilysin concentration may cause insulin resistance in susceptible people. There is a greater incidence of cardiovascular disease among overweight people with high NEP levels.


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