NSAIDs repress BACE1 gene promoter activity by activation of PPARgamma
M Sastre, S Roßner, N Bogdanovic, E Rosen, I Dewachter, P Borghgraef, B Evert, L Dumitrescu-Ozimek, D Thal, G Landreth, J Walter, T Klockgether, F van Leuven, M.T Heneka · Aktuelle Neurologie · 2005 · Heft 10
Bibliografische Angaben
Zusammenfassung
Epidemiological evidence suggests that non-steroidal anti-inflammatory drugs (NSAIDs) decrease the risk for Alzheimer's disease (AD). Certain NSAIDs can activate the peroxisome proliferator-activated receptor-gamma (PPARg), which is a nuclear transcriptional regulator. Here we show that PPARg depletion potentiates beta-secretase (BACE1) mRNA levels by increasing BACE1 gene promoter activity. Conversely, overexpression of PPARg as well as NSAIDs and PPARg activators, reduced BACE1 gene promoter activity. These results suggested that PPARg could be a repressor of BACE1. We then identified a PPARg responsive elemen…
