Abstract
Degeneration of neurons in Alzheimer's disease is mediated by beta-amyloid peptide by diverse mechanisms, which include a putative apoptotic component stimulated by unidentified signaling events. This report describes a novel beta-amyloid peptide-binding protein (denoted BBP) containing a G protein-coupling module. BBP is one member of a family of three proteins containing this conserved structure. The BBP subtype bound human beta-amyloid peptide in vitro with high affinity and specificity. Expression of BBP in cell culture induced caspase-dependent vulnerability to beta-amyloid peptide toxicity. Expression of a signaling-deficient dominant negative BBP mutant suppressed sensitivity of human Ntera-2 neurons to beta-amyloid peptide mediated toxicity. These findings suggest that BBP is a target of neurotoxic beta-amyloid peptide and provide new insight into the molecular pathophysiology of Alzheimer's disease.
MeSH terms
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Alzheimer Disease / metabolism
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Amino Acid Sequence
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Amyloid beta-Peptides / metabolism*
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Apoptosis*
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Binding Sites
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Binding, Competitive
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Blotting, Northern
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Brain / metabolism
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism*
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Caspases / metabolism
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Cell Line
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Cell Membrane / metabolism
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Cells, Cultured
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Conserved Sequence
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DNA, Complementary / metabolism
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Dose-Response Relationship, Drug
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GTP-Binding Proteins / metabolism*
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Gene Library
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Humans
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Immunoblotting
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In Situ Hybridization
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Kinetics
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Membrane Proteins
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Models, Biological
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Molecular Sequence Data
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Mutation
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Neurons / metabolism
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Peptides / metabolism*
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Protein Binding
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Protein Biosynthesis
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Protein Structure, Tertiary
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Recombinant Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Amino Acid
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Signal Transduction
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Tissue Distribution
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Two-Hybrid System Techniques
Substances
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Amyloid beta-Peptides
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Carrier Proteins
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DNA, Complementary
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Membrane Proteins
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Peptides
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Recombinant Proteins
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TM2D1 protein, human
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Tm2d1 protein, mouse
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Caspases
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GTP-Binding Proteins
Associated data
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GENBANK/AF353990
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GENBANK/AF353991
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GENBANK/AF353992
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GENBANK/AF353993