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Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1 conformation.
Nat. Med..09 26, 2004;10(10):1065-6.
Lleó A, Berezovska O, Herl L, Raju S, Deng A, Bacskai BJ, Frosch MP, Irizarry M, Hyman BT.
Alzheimer Research Unit, Massachusetts General Hospital, 114 16th St, Charlestown, Massachusetts 02129, USA.
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.