Hematopoetic Progenitors expressing CD10 are considered "Common Lymphoid Progenitors," which means they can differentiate into T, B or Natural Killer cells. CD10 is of use in hematological diagnosis since it is expressed by early B, pro-B and pre-B lymphocytes, and by lymph node germinal centers. Hematologic diseases in which it is positive include ALL, angioimmunoblastic T cell lymphoma, Burkitt lymphoma, CML in blast crisis (90%), diffuse large B-cell lymphoma (variable), follicular center cells (70%), hairy cell leukemia (10%), and myeloma (some). It tends to be negative in AML, CLL, mantle cell lymphoma, and marginal zone lymphoma. CD10 is found on non-T ALL cells, which derive from pre-B lymphocytes, and in germinal center-related non-Hodgkin lymphoma such as Burkitt lymphoma and follicular lymphoma, but not on leukemia cells or lymphomas, which originate in more mature B cells.
Neprilysin-deficient knockout mice show both Alzheimer's-like behavioral impairment and amyloid-beta deposition in the brain, providing strong evidence for the protein's association with the Alzheimer's disease process. Because neprilysin is thought to be the rate-limiting step in amyloid beta degradation, it has been considered a potential therapeutic target; compounds such as the peptide hormonesomatostatin have been identified that increase the enzyme's activity level. One hypothesis for the strong dependence of Alzheimer's incidence on age focuses on the declining production of somatostatin in the brains of elderly people, which thus depresses the activity of neprilysin and promotes aggregation of unprocessed amyloid beta. Declining neprilysin activity with increasing age may also be explained by oxidative damage, known to be a causative factor in Alzheimer's disease; higher levels of inappropriately oxidized neprilysin have been found in Alzheimer's patients compared to cognitively normal elderly people.
Associations have been observed between neprilysin expression and various types of cancer; however, the relationship between neprilysin expression and carcinogenesis remains obscure. In cancer biomarker studies, the neprilysin gene is often referred to as CD10 or CALLA. In some types of cancer, such as metastaticcarcinoma and some advanced melanomas, neprilysin is overexpressed; in other types, most notably lung cancers, neprilysin is downregulated, and thus unable to modulate the pro-growth autocrine signaling of cancer cells via secreted peptides such as mammalian homologs related to bombesin. Some plant extracts (methanol extracts of Ceropegia rupicola, Kniphofia sumarae, Plectranthus cf barbatus, and an aqueous extract of Pavetta longiflora) were found able to inhibit the enzymatic activity of neutral endopeptidase.
^Madani R, Poirier R, Wolfer DP, Welzl H, Groscurth P, Lipp HP, Lu B, El Mouedden M, Mercken M, Nitsch RM, Mohajeri MH (December 2006). "Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo". J. Neurosci. Res.84 (8): 1871–8. doi:10.1002/jnr.21074. PMID16998901.
^Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, Hosoki E, Kawashima-Morishima M, Lee HJ, Hama E, Sekine-Aizawa Y, Saido TC (February 2000). "Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition". Nat. Med.6 (2): 143–50. doi:10.1038/72237. PMID10655101.
^Wang DS, Iwata N, Hama E, Saido TC, Dickson DW (October 2003). "Oxidized neprilysin in aging and Alzheimer's disease brains". Biochem. Biophys. Res. Commun.310 (1): 236–41. doi:10.1016/j.bbrc.2003.09.003. PMID14511676.
^Sahli S, Stump B, Welti T, Schweizer WB, Diederich R, Blum-Kaelin D, Aebi JD, Böhm H-J (April 2005). "A New Class of Inhibitors for the Metalloprotease Neprilysin Based on a Central Imidazole Scaffold". Helvetica Chimica Acta88 (4): 707–730. doi:10.1002/hlca.200590050.
^Oefner C, Roques BP, Fournie-Zaluski MC, Dale GE (February 2004). "Structural analysis of neprilysin with various specific and potent inhibitors". Acta Crystallogr. D Biol. Crystallogr.60 (Pt 2): 392–6. doi:10.1107/S0907444903027410. PMID14747736.
^Velazquez EF, Yancovitz M, Pavlick A, Berman R, Shapiro R, Bogunovic D, O'Neill D, Yu YL, Spira J, Christos PJ, Zhou XK, Mazumdar M, Nanus DM, Liebes L, Bhardwaj N, Polsky D, Osman I (2007). "Clinical relevance of neutral endopeptidase (NEP/CD10) in melanoma". J Transl Med5: 2. doi:10.1186/1479-5876-5-2. PMC1770905. PMID17207277.