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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ferreira, Adriana Kelly, Brent L. Vassar, Robert |
| Description | Author Affiliation: Kelly BL ( Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.) |
| Abstract | Synaptic dysfunction is one of the earliest events in the pathogenesis of Alzheimer disease (AD). However, the molecular mechanisms underlying synaptic defects in AD are largely unknown. We report here that beta-amyloid (Abeta), the main component of senile plaques, induced a significant decrease in dynamin 1, a protein that is essential for synaptic vesicle recycling and, hence, for memory formation and information processing. The Abeta-induced dynamin 1 decrease occurred in the absence of overt synaptic loss and was also observed in the Tg2576 mouse model of AD. In addition, our results provided evidence that the Abeta-induced decrease in dynamin 1 was likely the result of a calpain-mediated cleavage of dynamin 1 protein and possibly the down-regulation of dynamin 1 gene expression. These data suggest a mechanism to explain the early cognitive loss without a major decline in synapse number observed in AD and propose a novel therapeutic target for AD intervention. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 36 |
| Volume Number | 280 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2005-09-09 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Alzheimer Disease Metabolism Physiopathology Amyloid Beta-Peptides Physiology Cognition Dynamin I Biosynthesis Hippocampus Neurons Pathology Genetics Animals Calpain Cells, Cultured Disease Models, Animal Mice Mice, Transgenic Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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