NEP
[variously termed as neutral endopeptidase-24.11 (NEP),
neprilysin, enkephalinase, EC3.4.24.11, common acute lymphoblastic
leukemia antigen (CALLA), CD10] is the key in vivo enzyme
degrading biopeptides Ab, substance-P and enkephalin in
brain; atrial natriuretic peptide, bradykinin and endothelin-1
in kidney. It is a 97 KDa ectoenzyme (mouse, rat, human
750-aa) with a large extracellular domain containing its
catalytic site, which can degrade Ab on cell surface. NEP
is ubiquitous but its high expression in brain is restricted
to striatum, olfactory tubercle, substantia nigra, choroids
plexes, endopeduncular nucleus, pontine nucleus, and cerebellum
and in many peripheral tissues, particularly in brush-border
membranes. The poor expression of NEP in the hippocampus
and cerebral cortex is reflected in the selective deposition
of Ab42 in these regions. NEP is also expressed in soluble
form in human plasma and cerebrospinal fluid. NEP can degrade
both synthetic and cell secreted Ab40 and Ab42 and may
be a good therapeutic target for the treatment of Alzheimer's
disease.
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