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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2000-9-21
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pubmed:abstractText |
The beta-amyloid precursor protein (beta-APP), which is involved in the pathogenesis of Alzheimer's disease, and the Notch receptor, which is responsible for critical signalling events during development, both undergo unusual proteolysis within their transmembrane domains by unknown gamma-secretases. Here we show that an affinity reagent designed to interact with the active site of gamma-secretase binds directly and specifically to heterodimeric forms of presenilins, polytopic proteins that are mutated in hereditary Alzheimer's and are known mediators of gamma-secretase cleavage of both beta-APP and Notch. These results provide evidence that heterodimeric presenilins contain the active site of gamma-secretase, and validate presenilins as principal targets for the design of drugs to treat and prevent Alzheimer's disease.
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pubmed:grant |
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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/Affinity Labels,
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/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane 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/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1465-7392
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
428-34
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10878808-Affinity Labels,
pubmed-meshheading:10878808-Alzheimer Disease,
pubmed-meshheading:10878808-Amyloid Precursor Protein Secretases,
pubmed-meshheading:10878808-Amyloid beta-Peptides,
pubmed-meshheading:10878808-Amyloid beta-Protein Precursor,
pubmed-meshheading:10878808-Animals,
pubmed-meshheading:10878808-Aspartic Acid Endopeptidases,
pubmed-meshheading:10878808-CHO Cells,
pubmed-meshheading:10878808-Cricetinae,
pubmed-meshheading:10878808-Dimerization,
pubmed-meshheading:10878808-Endopeptidases,
pubmed-meshheading:10878808-Humans,
pubmed-meshheading:10878808-Membrane Proteins,
pubmed-meshheading:10878808-Microsomes,
pubmed-meshheading:10878808-Molecular Weight,
pubmed-meshheading:10878808-Peptide Fragments,
pubmed-meshheading:10878808-Presenilin-1,
pubmed-meshheading:10878808-Presenilin-2,
pubmed-meshheading:10878808-Protease Inhibitors,
pubmed-meshheading:10878808-Protein Binding,
pubmed-meshheading:10878808-Protein Processing, Post-Translational,
pubmed-meshheading:10878808-Transfection
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pubmed:year |
2000
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pubmed:articleTitle |
Transition-state analogue inhibitors of gamma-secretase bind directly to presenilin-1.
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pubmed:affiliation |
Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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