Source:http://linkedlifedata.com/resource/pubmed/id/12857759
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
38
|
| pubmed:dateCreated |
2003-9-15
|
| pubmed:abstractText |
Generation of the amyloid peptide through proteolytic processing of the amyloid precursor protein by beta- and gamma-secretases is central to the etiology of Alzheimer's disease. beta-secretase, known more widely as the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), has been identified as a transmembrane aspartic proteinase, and its ectodomain has been reported to be cleaved and secreted from cells in a soluble form. The extracellular domains of many diverse proteins are known to be cleaved and secreted from cells by a process known as ectodomain shedding. Here we confirm that the ectodomain of BACE1 is secreted from cells and that this processing is up-regulated by agents that activate protein kinase C. A metalloproteinase is involved in the cleavage of BACE1 as hydroxamic acid-based metalloproteinase inhibitors abolish the release of shed BACE1. Using potent and selective inhibitors, we demonstrate that ADAM10 is a strong candidate for the BACE1 sheddase. In addition, we show that the BACE1 sheddase is distinct from alpha-secretase and, importantly, that inhibition of BACE1 shedding does not influence amyloid precursor protein processing at the beta-site.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid Precursor Protein Secretases,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/BACE1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
19
|
| pubmed:volume |
278
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
36264-8
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:12857759-Amyloid Precursor Protein Secretases,
pubmed-meshheading:12857759-Aspartic Acid Endopeptidases,
pubmed-meshheading:12857759-Binding Sites,
pubmed-meshheading:12857759-Blotting, Western,
pubmed-meshheading:12857759-Cell Line,
pubmed-meshheading:12857759-Dose-Response Relationship, Drug,
pubmed-meshheading:12857759-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:12857759-Endopeptidases,
pubmed-meshheading:12857759-Enzyme Activation,
pubmed-meshheading:12857759-Humans,
pubmed-meshheading:12857759-Hydroxamic Acids,
pubmed-meshheading:12857759-Inhibitory Concentration 50,
pubmed-meshheading:12857759-Models, Chemical,
pubmed-meshheading:12857759-Mutagenesis, Site-Directed,
pubmed-meshheading:12857759-Protein Binding,
pubmed-meshheading:12857759-Protein Kinase C,
pubmed-meshheading:12857759-Protein Structure, Tertiary,
pubmed-meshheading:12857759-Up-Regulation
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
Characterization of the ectodomain shedding of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1).
|
| pubmed:affiliation |
Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline Research & Development Limited, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, United Kingdom. Ishrut_2_Hussain@gsk.com
|
| pubmed:publicationType |
Journal Article
|