| pubmed-article:14504402 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:14504402 | lifeskim:mentions | umls-concept:C1167250 | lld:lifeskim |
| pubmed-article:14504402 | lifeskim:mentions | umls-concept:C0085151 | lld:lifeskim |
| pubmed-article:14504402 | lifeskim:mentions | umls-concept:C1454853 | lld:lifeskim |
| pubmed-article:14504402 | lifeskim:mentions | umls-concept:C0599894 | lld:lifeskim |
| pubmed-article:14504402 | lifeskim:mentions | umls-concept:C1709694 | lld:lifeskim |
| pubmed-article:14504402 | lifeskim:mentions | umls-concept:C1883712 | lld:lifeskim |
| pubmed-article:14504402 | pubmed:issue | 20 | lld:pubmed |
| pubmed-article:14504402 | pubmed:dateCreated | 2003-10-1 | lld:pubmed |
| pubmed-article:14504402 | pubmed:abstractText | beta-Secretase (BACE, Asp-2) is a transmembrane aspartic proteinase responsible for cleaving the amyloid precursor protein (APP) to generate the soluble ectodomain sAPPbeta and its C-terminal fragment CTFbeta. CTFbeta is subsequently cleaved by gamma-secretase to produce the neurotoxic/synaptotoxic amyloid-beta peptide (Abeta) that accumulates in Alzheimer's disease. Indirect evidence has suggested that amyloidogenic APP processing may preferentially occur in lipid rafts. Here, we show that relatively little wild-type BACE is found in rafts prepared from a human neuroblastoma cell line (SH-SY5Y) by using Triton X-100 as detergent. To investigate further the significance of lipid rafts in APP processing, a glycosylphosphatidylinositol (GPI) anchor has been added to BACE, replacing the transmembrane and C-terminal domains. The GPI anchor targets the enzyme exclusively to lipid raft domains. Expression of GPIBACE substantially up-regulates the secretion of both sAPPbeta and amyloid-beta peptide over levels observed from cells overexpressing wild-type BACE. This effect was reversed when the lipid rafts were disrupted by depleting cellular cholesterol levels. These results suggest that processing of APP to the amyloid-beta peptide occurs predominantly in lipid rafts and that BACE is the rate-limiting enzyme in this process. The processing of the APP695 isoform by GPI-BACE was up-regulated 20-fold compared with wild-type BACE, whereas only a 2-fold increase in the processing of APP751/770 was seen, implying a differential compartmentation of the APP isoforms. Changes in the local membrane environment during aging may facilitate the cosegregation of APP and BACE leading to increased beta-amyloid production. | lld:pubmed |
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| pubmed-article:14504402 | pubmed:language | eng | lld:pubmed |
| pubmed-article:14504402 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:14504402 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:14504402 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:14504402 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:14504402 | pubmed:issn | 0027-8424 | lld:pubmed |
| pubmed-article:14504402 | pubmed:author | pubmed-author:DingwallColin... | lld:pubmed |
| pubmed-article:14504402 | pubmed:author | pubmed-author:HooperNigel... | lld:pubmed |
| pubmed-article:14504402 | pubmed:author | pubmed-author:TurnerAnthony... | lld:pubmed |
| pubmed-article:14504402 | pubmed:author | pubmed-author:HussainIshrut... | lld:pubmed |
| pubmed-article:14504402 | pubmed:author | pubmed-author:CordyJoanna... | lld:pubmed |
| pubmed-article:14504402 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:14504402 | pubmed:day | 30 | lld:pubmed |
| pubmed-article:14504402 | pubmed:volume | 100 | lld:pubmed |
| pubmed-article:14504402 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:14504402 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:14504402 | pubmed:pagination | 11735-40 | lld:pubmed |
| pubmed-article:14504402 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:14504402 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:14504402 | pubmed:articleTitle | Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta-site processing of the amyloid precursor protein. | lld:pubmed |
| pubmed-article:14504402 | pubmed:affiliation | Proteolysis Research Group, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom. | lld:pubmed |
| pubmed-article:14504402 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:14504402 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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