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ELISA analysis of β-secretase cleavage of the Swedish amyloid precursor protein in the secretory and endocytic pathways

dc.contributor.authorSteinhilb, Michelle L.en_US
dc.contributor.authorTurner, R. Scotten_US
dc.contributor.authorGaut, James R.en_US
dc.date.accessioned2010-04-01T15:53:47Z
dc.date.available2010-04-01T15:53:47Z
dc.date.issued2002-03-15en_US
dc.identifier.citationSteinhilb, Michelle L . ; Turner, R. Scott; Gaut, James R . (2002). "ELISA analysis of β-secretase cleavage of the Swedish amyloid precursor protein in the secretory and endocytic pathways." Journal of Neurochemistry 80(6): 1019-1028. <http://hdl.handle.net/2027.42/66393>en_US
dc.identifier.issn0022-3042en_US
dc.identifier.issn1471-4159en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/66393
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=11953452&dopt=citationen_US
dc.description.abstractLimiting beta amyloid (Aβ) production could become an important therapeutic target in Alzheimer's disease (AD). Aβ is derived by the sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases. A double missense mutation in APP found in a Swedish pedigree (APPsw) elevates Aβ40 and Aβ42 production. Aβ production and, therefore, β-secretase cleavage of APPsw reportedly occur in the endoplasmic reticulum (ER), Golgi and endocytic compartments. However, the relative contribution of β-secretase cleavage occurring in each compartment has not been determined. Experiments described here use a novel ELISA to measure the β-cleaved product, APPswβ. Using this ELISA, we provide new information regarding the relative amount of β-secretase cleavage of APPsw that occurs in secretory and endocytic pathways. Using a dilysine retrieval motif to retain APPsw in the ER, we discovered that less than 15% of the β-secretase cleavage was still detected. Experiments utilizing endocytosis-impaired mutants of APPsw revealed that little or no β-secretase cleavage of APPsw appears to take place through endocytosis. Surprisingly, deletion of the entire cytoplasmic tail increased both APPswβ and Aβ secretion, suggesting that protein interactions with this region normally impede β-secretase cleavage. These results suggest that APPsw is cleaved by β-secretase late in the secretory pathway.en_US
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dc.format.extent3110 bytes
dc.format.mimetypeapplication/pdf
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dc.publisherBlackwell Science, Ltden_US
dc.rights2002 International Society for Neurochemistryen_US
dc.subject.otherAlzheimer's Diseaseen_US
dc.subject.otherBACEen_US
dc.subject.otherβ-Secretaseen_US
dc.subject.otherEndoplasmic Reticulumen_US
dc.titleELISA analysis of β-secretase cleavage of the Swedish amyloid precursor protein in the secretory and endocytic pathwaysen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelNeurosciencesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationum* Institute of Gerontology and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, USAen_US
dc.contributor.affiliationum† Department of Neurology, University of Michigan Medical Center, Ann Arbor, Michigan, USAen_US
dc.contributor.affiliationum† Veterans Affairs Medical Center Geriatric Research, Education, and Clinical Center, Ann Arbor, Michigan, USAen_US
dc.identifier.pmid11953452en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/66393/1/j.0022-3042.2002.00764.x.pdf
dc.identifier.doi10.1046/j.0022-3042.2002.00764.xen_US
dc.identifier.sourceJournal of Neurochemistryen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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