Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1 conformation.

Lleó, Alberto; Berezovska, Oksana; Herl, Lauren; Raju, Susan; Deng, Amy; Bacskai, Brian J; Frosch, Matthew P; Irizarry, Michael et al. · Nat Med · 2004

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.

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