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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5669
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pubmed:dateCreated |
2004-4-16
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pubmed:databankReference |
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pubmed:abstractText |
Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal toxicity in Alzheimer's disease (AD). Here, we demonstrate that Abeta-binding alcohol dehydrogenase (ABAD) is a direct molecular link from Abeta to mitochondrial toxicity. Abeta interacts with ABAD in the mitochondria of AD patients and transgenic mice. The crystal structure of Abeta-bound ABAD shows substantial deformation of the active site that prevents nicotinamide adenine dinucleotide (NAD) binding. An ABAD peptide specifically inhibits ABAD-Abeta interaction and suppresses Abeta-induced apoptosis and free-radical generation in neurons. Transgenic mice overexpressing ABAD in an Abeta-rich environment manifest exaggerated neuronal oxidative stress and impaired memory. These data suggest that the ABAD-Abeta interaction may be a therapeutic target in AD.
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pubmed:grant |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1095-9203
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pubmed:author |
pubmed-author:ArancioOttavioO,
pubmed-author:CaspersenCasperC,
pubmed-author:ChaneyMichaelM,
pubmed-author:ChangLinL,
pubmed-author:ChenXiX,
pubmed-author:CirilliMaurizioM,
pubmed-author:EnoNN,
pubmed-author:Gunn-MooreFrankF,
pubmed-author:KuppusamyPeriannanP,
pubmed-author:LiuShuminS,
pubmed-author:LueLih-FenLF,
pubmed-author:LustbaderJoyce WJW,
pubmed-author:PollakSusanS,
pubmed-author:SternDavidD,
pubmed-author:TakumaKazuhiroK,
pubmed-author:TrincheseFabrizioF,
pubmed-author:WalkerDouglas GDG,
pubmed-author:WangNingN,
pubmed-author:XuHong WeiHW,
pubmed-author:YanShirley ShiDuSS,
pubmed-author:ZewierZay LZL
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
304
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
448-52
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15087549-3-Hydroxyacyl CoA Dehydrogenases,
pubmed-meshheading:15087549-Aged,
pubmed-meshheading:15087549-Aged, 80 and over,
pubmed-meshheading:15087549-Alzheimer Disease,
pubmed-meshheading:15087549-Amino Acid Sequence,
pubmed-meshheading:15087549-Amyloid beta-Peptides,
pubmed-meshheading:15087549-Animals,
pubmed-meshheading:15087549-Binding Sites,
pubmed-meshheading:15087549-Brain,
pubmed-meshheading:15087549-Brain Chemistry,
pubmed-meshheading:15087549-Carrier Proteins,
pubmed-meshheading:15087549-Cells, Cultured,
pubmed-meshheading:15087549-Cerebral Cortex,
pubmed-meshheading:15087549-Crystallization,
pubmed-meshheading:15087549-DNA Fragmentation,
pubmed-meshheading:15087549-Hippocampus,
pubmed-meshheading:15087549-Humans,
pubmed-meshheading:15087549-Learning,
pubmed-meshheading:15087549-Memory,
pubmed-meshheading:15087549-Mice,
pubmed-meshheading:15087549-Mice, Transgenic,
pubmed-meshheading:15087549-Microscopy, Confocal,
pubmed-meshheading:15087549-Microscopy, Immunoelectron,
pubmed-meshheading:15087549-Mitochondria,
pubmed-meshheading:15087549-Models, Molecular,
pubmed-meshheading:15087549-Molecular Sequence Data,
pubmed-meshheading:15087549-Mutation,
pubmed-meshheading:15087549-NAD,
pubmed-meshheading:15087549-Neurons,
pubmed-meshheading:15087549-Protein Binding,
pubmed-meshheading:15087549-Protein Conformation,
pubmed-meshheading:15087549-Reactive Oxygen Species
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pubmed:year |
2004
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pubmed:articleTitle |
ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease.
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pubmed:affiliation |
Center for Reproductive Sciences and Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, 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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