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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2005-5-5
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pubmed:abstractText |
Increased Abeta42 production has been linked to the development of Alzheimer disease. We now identify a number of compounds that raise Abeta42. Among the more potent Abeta42-raising agents identified are fenofibrate, an antilipidemic agent, and celecoxib, a COX-2-selective NSAID. Many COX-2-selective NSAIDs tested raised Abeta42, including multiple COX-2-selective derivatives of two Abeta42-lowering NSAIDs. Compounds devoid of COX activity and the endogenous isoprenoids FPP and GGPP also raised Abeta42. These compounds seem to target the gamma-secretase complex, increasing gamma-secretase-catalyzed production of Abeta42 in vitro. Short-term in vivo studies show that two Abeta42-raising compounds increase Abeta42 levels in the brains of mice. The elevations in Abeta42 by these compounds are comparable to the increases in Abeta42 induced by Alzheimer disease-causing mutations in the genes encoding amyloid beta protein precursor and presenilins, raising the possibility that exogenous compounds or naturally occurring isoprenoids might increase Abeta42 production in humans.
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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/Amyloid Precursor Protein Secretases,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/BACE1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Fenofibrate,
http://linkedlifedata.com/resource/pubmed/chemical/Hypolipidemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/celecoxib,
http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1078-8956
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pubmed:author |
pubmed-author:AnastasiadisPanos ZPZ,
pubmed-author:BeardJennyJ,
pubmed-author:DasPritamP,
pubmed-author:DodsonMarkM,
pubmed-author:EriksenJason LJL,
pubmed-author:FauqAbdulA,
pubmed-author:GoldeTodd ETE,
pubmed-author:KacheRajashakerR,
pubmed-author:KhanMurad AMA,
pubmed-author:KooEdward HEH,
pubmed-author:KukarThomasT,
pubmed-author:LaddThomasT,
pubmed-author:MeritSamiS,
pubmed-author:MurphyMichael PaulMP,
pubmed-author:OzolsVictor VVV,
pubmed-author:SagiSarah ASA,
pubmed-author:SmithTawnya ETE,
pubmed-author:WeggenSaschaS
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pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
545-50
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15834426-Alzheimer Disease,
pubmed-meshheading:15834426-Amyloid Precursor Protein Secretases,
pubmed-meshheading:15834426-Amyloid beta-Peptides,
pubmed-meshheading:15834426-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:15834426-Aspartic Acid Endopeptidases,
pubmed-meshheading:15834426-Brain,
pubmed-meshheading:15834426-Cell Line,
pubmed-meshheading:15834426-Cyclooxygenase Inhibitors,
pubmed-meshheading:15834426-Endopeptidases,
pubmed-meshheading:15834426-Enzyme Activation,
pubmed-meshheading:15834426-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:15834426-Female,
pubmed-meshheading:15834426-Fenofibrate,
pubmed-meshheading:15834426-Humans,
pubmed-meshheading:15834426-Hypolipidemic Agents,
pubmed-meshheading:15834426-Immunoprecipitation,
pubmed-meshheading:15834426-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15834426-Mass Spectrometry,
pubmed-meshheading:15834426-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15834426-Pyrazoles,
pubmed-meshheading:15834426-Sulfonamides,
pubmed-meshheading:15834426-Transfection,
pubmed-meshheading:15834426-rho-Associated Kinases,
pubmed-meshheading:15834426-rhoA GTP-Binding Protein
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pubmed:year |
2005
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pubmed:articleTitle |
Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production.
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pubmed:affiliation |
Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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