1. G protein-mediated neuronal DNA fragmentation induced by familial Alzheimer's disease-associated mutants of APP.
- Author
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Yamatsuji T, Matsui T, Okamoto T, Komatsuzaki K, Takeda S, Fukumoto H, Iwatsubo T, Suzuki N, Asami-Odaka A, Ireland S, Kinane TB, Giambarella U, and Nishimoto I
- Subjects
- Alzheimer Disease metabolism, Amyloid beta-Peptides metabolism, Amyloid beta-Protein Precursor chemistry, Amyloid beta-Protein Precursor genetics, Animals, Apoptosis, Base Sequence, Culture Media, Conditioned, Humans, Hybrid Cells, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutation, Neurons cytology, Peptide Fragments metabolism, Rats, Transfection, Alzheimer Disease genetics, Amyloid beta-Protein Precursor physiology, DNA metabolism, GTP-Binding Proteins physiology, Neurons metabolism, Nucleosomes metabolism
- Abstract
Missense mutations in the 695-amino acid form of the amyloid precursor protein (APP695) cosegregate with disease phenotype in families with dominantly inherited Alzheimer's disease. These mutations convert valine at position 642 to isoleucine, phenylalanine, or glycine. Expression of these mutant proteins, but not of normal APP695, was shown to induce nucleosomal DNA fragmentation in neuronal cells. Induction of DNA fragmentation required the cytoplasmic domain of the mutants and appeared to be mediated by heterotrimeric guanosine triphosphate-binding proteins (G proteins).
- Published
- 1996
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