Aberrant presenilin-1 expression downregulates LDL receptor-related protein (LRP): is LRP central to Alzheimer's disease pathogenesis?
| Autor: | Peter St George-Hyslop, George A. Carlson, Robert A. Orlando, Eliezer Masliah, David Westaway, Margaret Mallory, Edward Rockenstein, Emily Van Uden |
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| Rok vydání: | 1999 |
| Předmět: |
Apolipoprotein E
Genetically modified mouse Transcription Genetic Mice Inbred Strains Mice Transgenic Neocortex medicine.disease_cause Hippocampus Presenilin Pathogenesis Cellular and Molecular Neuroscience Mice Alzheimer Disease Interneurons mental disorders medicine Amyloid precursor protein Presenilin-1 Animals Humans RNA Messenger Receptors Immunologic Molecular Biology Crosses Genetic Neurons Mutation biology Pyramidal Cells Membrane Proteins Cell Biology Transfection Molecular biology Mice Inbred C57BL Gene Expression Regulation Receptors LDL LDL receptor Cancer research biology.protein lipids (amino acids peptides and proteins) Somatostatin Low Density Lipoprotein Receptor-Related Protein-1 |
| Zdroj: | Molecular and cellular neurosciences. 14(2) |
| ISSN: | 1044-7431 |
| Popis: | Low density lipoprotein receptor-related protein (LRP) polymorphisms have recently been associated with an increased susceptibility of Alzheimer's disease (AD). Furthermore, LRP has been linked to molecules that confer susceptibility to AD (apolipoprotein E, alpha-2-macroglobulin, amyloid precursor protein), previously with the exception of the presenilins. Here we report that aberrant presenilin-1 expression in vivo and in vitro downregulates LRP. Specifically, transgenic mice overexpressing the M146L or L286V presenilin-1 mutation show decreased levels of LRP expression in neuronal populations where presenilin-1 and LRP are closely colocalized or coexpressed. Moreover, cell lines transfected with presenilin-1 also expressed decreased levels of LRP. These findings suggest that LRP may be central to AD pathogenesis since all proteins genetically associated with AD can now be linked via a single pathway to LRP. |
| Databáze: | OpenAIRE |
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