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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lanteigne, Anne-marie Brichard, Vincent Thériault, Peter Larocque, Daniel Jodoin, Rachel Cluff, Christopher Préfontaine, Paul Rivest, Serge Palmantier, Rémi Filali, Mohammed Hallé, Maxime Pilorget, Anthony Lampron, Antoine Tribout-jover, Pascale Michaud, Jean-philippe |
| Description | Author Affiliation: Michaud JP ( Neuroscience Laboratory, Department of Molecular Medicine, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, QC, Canada G1V 4G2.); |
| Abstract | Alzheimer's disease (AD) is the most common cause of dementia worldwide. The pathogenesis of this neurodegenerative disease, currently without curative treatment, is associated with the accumulation of amyloid ß (Aß) in brain parenchyma and cerebral vasculature. AD patients are unable to clear this toxic peptide, leading to Aß accumulation in their brains and, presumably, the pathology associated with this devastating disease. Compounds that stimulate the immune system to clear Aß may therefore have great therapeutic potential in AD patients. Monophosphoryl lipid A (MPL) is an LPS-derived Toll-like receptor 4 agonist that exhibits unique immunomodulatory properties at doses that are nonpyrogenic. We show here that repeated systemic injections of MPL, but not LPS, significantly improved AD-related pathology in APP(swe)/PS1 mice. MPL treatment led to a significant reduction in Aß load in the brain of these mice, as well as enhanced cognitive function. MPL induced a potent phagocytic response by microglia while triggering a moderate inflammatory reaction. Our data suggest that the Toll-like receptor 4 agonist MPL may be a treatment for AD. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 5 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Alzheimer Disease Prevention & Control Brain Drug Effects Lipid A Analogs & Derivatives Toll-Like Receptor 4 Agonists Metabolism Pathology Amyloid Beta-Protein Precursor Genetics Animals Blotting, Western Cell Line Cytokines Gene Expression HEK293 Cells Immunity, Innate Ligands Administration & Dosage Therapeutic Use Lipopolysaccharides Pharmacology Mice Mice, Inbred C57BL Mice, Transgenic Microglia Cytology Microscopy, Fluorescence Phagocytosis Presenilin-1 Reverse Transcriptase Polymerase Chain Reaction Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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