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Alzheimers AND glitazone

Martina Hieke, Julia Ness, Ramona Steri, Michaela Dittrich, Christine Greiner, Oliver Werz, Karlheinz Baumann, Manfred Schubert-Zsilavecz, Sascha Weggen, Heiko Zettl
We present a novel class of dual modulators of gamma-secretase and peroxisome proliferator-activated receptor gamma (PPARgamma) based on the structure of 2-(bis(phenethoxy)pyrimidine-2-ylthio)hexanoic acid 8 (IC(50)(Abeta42) = 22.8 microM, EC(50)(PPARgamma) = 8.3 microM). The modulation of both targets with approved drugs (i.e., amyloid-beta 42 (Abeta42)-lowering NSAIDs for gamma-secretase and glitazones for PPARgamma) has demonstrated beneficial effects in in vitro and in vivo models of Alzheimer's disease (AD)...
June 24, 2010: Journal of Medicinal Chemistry
Mary N Haan
A number of well-designed epidemiological studies have linked type 2 diabetes mellitus (T2DM) with an increased risk of Alzheimer's disease (AD). Several mechanisms could help to explain this proposed link, including insulin and insulin resistance, inflammatory cytokines, and oxidative stress. Obesity or physical inactivity might also influence AD through effects on hypertension, insulin sensitivity or inflammation. Typical AD pathology, such as amyloid-beta deposits, might be exacerbated by insulin dysregulation, T2DM itself, or microvascular disease that is a consequence of T2DM...
March 2006: Nature Clinical Practice. Neurology
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