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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6761
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pubmed:dateCreated |
1999-12-16
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pubmed:databankReference |
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pubmed:abstractText |
Mutations in the gene encoding the amyloid protein precursor (APP) cause autosomal dominant Alzheimer's disease. Cleavage of APP by unidentified proteases, referred to as beta- and gamma-secretases, generates the amyloid beta-peptide, the main component of the amyloid plaques found in Alzheimer's disease patients. The disease-causing mutations flank the protease cleavage sites in APP and facilitate its cleavage. Here we identify a new membrane-bound aspartyl protease (Asp2) with beta-secretase activity. The Asp2 gene is expressed widely in brain and other tissues. Decreasing the expression of Asp2 in cells reduces amyloid beta-peptide production and blocks the accumulation of the carboxy-terminal APP fragment that is created by beta-secretase cleavage. Solubilized Asp2 protein cleaves a synthetic APP peptide substrate at the beta-secretase site, and the rate of cleavage is increased tenfold by a mutation associated with early-onset Alzheimer's disease in Sweden. Thus, Asp2 is a new protein target for drugs that are designed to block the production of amyloid beta-peptide peptide and the consequent formation of amyloid plaque in Alzheimer's disease.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid Precursor Protein Secretases,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Protein Precursor,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/BACE1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BACE2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bace1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0028-0836
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pubmed:author |
pubmed-author:ApauRR,
pubmed-author:BienkowskiM JMJ,
pubmed-author:BrashierJ RJR,
pubmed-author:CarterD BDB,
pubmed-author:GurneyM EME,
pubmed-author:HeinriksonR LRL,
pubmed-author:MathewsW RWR,
pubmed-author:MiaoHH,
pubmed-author:ParodiL ALA,
pubmed-author:PauleyA MAM,
pubmed-author:ShuckM EME,
pubmed-author:StratmanN CNC,
pubmed-author:TomasselliA GAG,
pubmed-author:ToryM CMC,
pubmed-author:YaoSS
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pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
402
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
533-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10591213-Alzheimer Disease,
pubmed-meshheading:10591213-Amino Acid Sequence,
pubmed-meshheading:10591213-Amyloid Precursor Protein Secretases,
pubmed-meshheading:10591213-Amyloid beta-Peptides,
pubmed-meshheading:10591213-Amyloid beta-Protein Precursor,
pubmed-meshheading:10591213-Animals,
pubmed-meshheading:10591213-Aspartic Acid Endopeptidases,
pubmed-meshheading:10591213-CHO Cells,
pubmed-meshheading:10591213-Caenorhabditis elegans,
pubmed-meshheading:10591213-Cell Line,
pubmed-meshheading:10591213-Cell Membrane,
pubmed-meshheading:10591213-Cricetinae,
pubmed-meshheading:10591213-Endopeptidases,
pubmed-meshheading:10591213-Enzyme Inhibitors,
pubmed-meshheading:10591213-Humans,
pubmed-meshheading:10591213-Mice,
pubmed-meshheading:10591213-Molecular Sequence Data,
pubmed-meshheading:10591213-Mutation,
pubmed-meshheading:10591213-Oligonucleotides, Antisense,
pubmed-meshheading:10591213-Recombinant Proteins,
pubmed-meshheading:10591213-Tissue Distribution,
pubmed-meshheading:10591213-Transfection,
pubmed-meshheading:10591213-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity.
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pubmed:affiliation |
Cell & Molecular Biology, Pharmacia & Upjohn, Inc., Kalamazoo, MI 49007, USA. riqiang.yan@am.pnu.com
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pubmed:publicationType |
Journal Article
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