{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:16:40Z","timestamp":1773299800021,"version":"3.50.1"},"reference-count":50,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,4,1]]},"abstract":"<jats:p>In the amyloidogenic pathway, the APP (amyloid precursor protein) is proteolytically processed by the \u03b2- and \u03b3-secretases to release the A\u03b2 (amyloid-\u03b2) peptide that is neurotoxic and aggregates in the brains of patients suffering from Alzheimer's disease. In the non-amyloidogenic pathway, APP is cleaved by \u03b1-secretase within the A\u03b2 domain, precluding deposition of intact A\u03b2 peptide. The cellular form of the PrPC (prion protein) undergoes reactive oxygen species-mediated \u03b2-cleavage within the copper-binding octapeptide repeats or, alternatively, \u03b1-cleavage within the central hydrophobic neurotoxic domain. In addition, PrPC is shed from the membrane by the action of a zinc metalloprotease. Members of the ADAM (a disintegrin and metalloproteinase) family of zinc metalloproteases, notably ADAM10 and TACE (ADAM17) display \u03b1-secretase activity towards APP and appear to be responsible for the \u03b1-cleavage of PrPC. The amyloidogenic cleavage of APP by the \u03b2- and \u03b3-secretases appears to occur preferentially in cholesterol-rich lipid rafts, while the conversion of PrPC into the infectious form PrPSc also appears to occur in these membrane domains.<\/jats:p>","DOI":"10.1042\/bst0330335","type":"journal-article","created":{"date-parts":[[2005,4,5]],"date-time":"2005-04-05T13:39:07Z","timestamp":1112708347000},"page":"335-338","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein"],"prefix":"10.1042","volume":"33","author":[{"given":"N.M.","family":"Hooper","sequence":"first","affiliation":[{"name":"Proteolysis Research Group, School of Biochemistry and Microbiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT, U.K."}]}],"member":"288","published-online":{"date-parts":[[2005,4,1]]},"reference":[{"key":"2021111718352724600_B1","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1126\/science.1067122","volume":"9","author":"Taylor","year":"2002","journal-title":"Science"},{"key":"2021111718352724600_B2","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1073\/pnas.95.23.13363","volume":"95","author":"Prusiner","year":"1998","journal-title":"Proc. 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