Membrane-anchored Aβ accelerates amyloid formation and exacerbates amyloid-associated toxicity in mice
| Autor: | Frank Baumann, Amudha Nagarathinam, Claudia Schäfer, Mathias Jucker, Matthias Staufenbiel, Martin Jeffrey, Gillian McGovern, Philip Höflinger, Anika Bühler |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Genetically modified mouse
Amyloid Blotting Western Plaque Amyloid Peptide Biology Phosphatidylinositols metabolism [Cell Membrane] Mice In vivo genetics [Amyloid beta-Peptides] Animals Humans Biotinylation ddc:610 Benzothiazoles pathology [Plaque Amyloid] Cellular compartment Fluorescent Dyes pathology [Inflammation] Inflammation chemistry.chemical_classification Amyloid beta-Peptides thioflavin T General Neuroscience Cell Membrane P3 peptide Articles Immunohistochemistry In vitro pathology [Cell Membrane] Cell biology toxicity [Amyloid beta-Peptides] chemistry [Type C Phospholipases] Mice Inbred C57BL Thiazoles HEK293 Cells Biochemistry chemistry pharmacology [Amyloid beta-Peptides] Type C Phospholipases Toxicity Endopeptidase K chemistry [Endopeptidase K] |
| Zdroj: | The journal of neuroscience 33(49), 19284-19294 (2013). doi:10.1523/JNEUROSCI.2542-13.2013 |
| DOI: | 10.1523/JNEUROSCI.2542-13.2013 |
| Popis: | Pathological, genetic, and biochemical hallmarks of Alzheimer's disease (AD) are linked to amyloid-β (Aβ) peptide aggregation. Especially misfolded Aβ42peptide is sufficient to promote amyloid plaque formation. However, the cellular compartment facilitating the conversion of monomeric Aβ to aggregated toxic Aβ species remains unknown.In vitromodels suggest lipid membranes to be the driving force of Aβ conversion. To this end, we generated two novel mouse models, expressing either membrane-anchored or nonanchored versions of the human Aβ42peptide. Strikingly, membrane-anchored Aβ42robustly accelerated Aβ deposition and exacerbated amyloid-associated toxicity upon crossing with Aβ precursor protein transgenic mice. Thesein vivofindings support the hypothesis that Aβ–membrane interactions play a pivotal role in early-onset AD as well as neuronal damage and provide evidence to study Aβ–membrane interactions as therapeutic targets. |
| Databáze: | OpenAIRE |
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