Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1 conformation.
basic_science · Level V
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Abstract
Recent reports suggest that some commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) unexpectedly shift the cleavage products of amyloid precursor protein (APP) to shorter, less fibrillogenic forms, although the underlying mechanism remains unknown. We now demonstrate, using a fluorescence resonance energy transfer method, that Abeta(42)-lowering NSAIDs specifically affect the proximity between APP and presenilin 1 and alter presenilin 1 conformation both in vitro and in vivo, suggesting a novel allosteric mechanism of action.
Medical subject headings
- Amyloid beta-Peptides
- Anti-Inflammatory Agents, Non-Steroidal
- Carrier Proteins
- Endopeptidases
- Membrane Proteins
- Models, Molecular
- Peptide Fragments