{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T18:11:31Z","timestamp":1776795091633,"version":"3.51.2"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,12,20]],"date-time":"2011-12-20T00:00:00Z","timestamp":1324339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer's disease (AD) is characterized by senile plaques caused by amyloid\u2010\u03b2 peptide (A\u03b2) accumulation. It has been reported that A\u03b2 generation and accumulation occur in membrane microdomains, called<jats:italic>lipid rafts<\/jats:italic>, which are enriched in cholesterol and glycosphingolipids. Moreover, the ablation of cholesterol metabolism has been implicated in AD. Neprilysin (NEP), a neutral endopeptidase, is one of the major A\u03b2\u2010degrading enzymes in the brain. Activation of NEP is a possible therapeutic target. However, it remains unknown whether the activity of NEP is regulated by its association with lipid rafts. Here we show that only the mature form of NEP, which has been glycosylated in the Golgi, exists in lipid rafts, where it is directly associated with phosphatidylserine. Moreover, the localization of NEP in lipid rafts is enhanced by its dimerization, as shown using the NEP E403C homodimerization mutant. However, the protease activities of the mature form of NEP, as assessed by in vitro peptide hydrolysis, did not differ between lipid rafts and nonlipid rafts. We conclude that cholesterol and other lipids regulate the localization of mature NEP to lipid rafts, where the substrate A\u03b2 accumulates but does not modulate the protease activity of NEP. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22796","type":"journal-article","created":{"date-parts":[[2011,12,20]],"date-time":"2011-12-20T06:50:45Z","timestamp":1324363845000},"page":"870-877","source":"Crossref","is-referenced-by-count":12,"title":["Localization of mature neprilysin in lipid 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