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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
2000-11-20
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pubmed:abstractText |
Alzheimer's disease is characterised by the progressive deposition of the 4 kDa beta-amyloid peptide (A beta) in extracellular senile plaques in the brain. A beta is derived by proteolytic cleavage of the amyloid precursor protein (APP) by various proteinases termed secretases. alpha-Secretase is inhibited by hydroxamate-based zinc metalloproteinase inhibitors such as batimastat with I50 values in the low micromolar range, and displays many properties in common with the secretase that releases angiotensin converting enzyme. A cell impermeant biotinylated derivative of one such inhibitor completely blocked the release of APP from the surface of neuronal cells, indicating that alpha-secretase cleaves APP at the cell-surface. A range of hydroxamate-based compounds have been used to distinguish between alpha-secretase and tumour necrosis factor-alpha convertase, a member of the ADAMs (a disintegrin and metalloproteinase-like) family of zinc metalloproteinases. Recent data suggests that the presenilins may be aspartyl proteinases with the specificity of gamma-secretase. Although APP and the presenilins are present in detergent-insoluble, cholesterol- and glycosphingolipid-rich lipid rafts, they do not behave as typical lipid raft proteins, and thus it is unclear whether these membrane domains are the sites for proteolytic processing of APP.
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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/ADAM Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid Precursor Protein Secretases,
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/BB 2116,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PSEN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PSEN2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylalanine,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Thiophenes,
http://linkedlifedata.com/resource/pubmed/chemical/batimastat,
http://linkedlifedata.com/resource/pubmed/chemical/marimastat,
http://linkedlifedata.com/resource/pubmed/chemical/tumor necrosis factor-alpha...
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pubmed:status |
MEDLINE
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pubmed:issn |
0065-2598
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
477
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
379-90
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10849764-ADAM Proteins,
pubmed-meshheading:10849764-Alzheimer Disease,
pubmed-meshheading:10849764-Amyloid Precursor Protein Secretases,
pubmed-meshheading:10849764-Amyloid beta-Protein Precursor,
pubmed-meshheading:10849764-Animals,
pubmed-meshheading:10849764-Aspartic Acid Endopeptidases,
pubmed-meshheading:10849764-Biotinylation,
pubmed-meshheading:10849764-Endopeptidases,
pubmed-meshheading:10849764-Humans,
pubmed-meshheading:10849764-Hydroxamic Acids,
pubmed-meshheading:10849764-Membrane Lipids,
pubmed-meshheading:10849764-Membrane Proteins,
pubmed-meshheading:10849764-Metalloendopeptidases,
pubmed-meshheading:10849764-Nerve Tissue Proteins,
pubmed-meshheading:10849764-Phenylalanine,
pubmed-meshheading:10849764-Presenilin-1,
pubmed-meshheading:10849764-Presenilin-2,
pubmed-meshheading:10849764-Protease Inhibitors,
pubmed-meshheading:10849764-Rats,
pubmed-meshheading:10849764-Thiophenes
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pubmed:year |
2000
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pubmed:articleTitle |
The role of proteolysis in Alzheimer's disease.
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pubmed:affiliation |
School of Biochemistry and Molecular Biology, University of Leeds, UK.
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pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
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