Browsing by Author "Institut des Biomolecules Max Mousseron"

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    Chemical and bioactivity evaluation of the bark of Neonauclea purpurea
    (2012-05-14) Netiya Karaket; Kanyaratt Supaibulwatana; Supatsara Ounsuk; Valérie Bultel-Poncé; Van Cuong Pham; Bernard Bodo; Mahidol University; Museum National d'Histoire Naturelle; Institut des Biomolecules Max Mousseron; Vietnamese Academy of Science and Technology Institute of Chemistry
    Bioassay-guided fractionation of the MeOH extract from the stem bark of Neonauclea purpurea used in traditional medicine, resulted in the isolation of 2 indole alkaloids, cadambine (1) and α-dihydrocadambine (2), as well as a quinolic compound, 2,6-dimethoxy-1,4-benzoquinone (3). Antimalarial activity evaluation showed that compounds 2 and 3 exhibited mild in vitro antimalarial activity against Plasmodium falciparum, the chloroquine-resistant strain K1 with IC 50 values of 6.6 and 11.3 μM, respectively. Compounds 1 and 2 showed no cytotoxicity to monkey (Vero) cells, but compound 3 showed weak cytotoxicity with an IC 50 value of 1.19 μM.
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    Melatonin stimulates the nonamyloidogenic processing of βaPP through the positive transcriptional regulation of ADAM10 and ADAM17
    (2015-01-01) Mayuri Shukla; Htut Htut Htoo; Phitchayapak Wintachai; Jean Francois Hernandez; Claire Dubois; Rolf Postina; Huaxi Xu; Frédéric Checler; Duncan R. Smith; Piyarat Govitrapong; Bruno Vincent; Mahidol University; Institut des Biomolecules Max Mousseron; Universite de Sherbrooke; Johannes Gutenberg Universitat Mainz; Xiamen University; Sanford Burnham Prebys Medical Discovery Institute; Universite Nice Sophia Antipolis; CNRS Centre National de la Recherche Scientifique
    © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Melatonin controls many physiological functions including regulation of the circadian rhythm and clearance of free radicals and neuroprotection. Importantly, melatonin levels strongly decrease as we age and patients with Alzheimer's disease (AD) display lower melatonin than age-matched controls. Several studies have reported that melatonin can reduce aggregation and toxicity of amyloid-β peptides that are produced from the β-amyloid precursor protein (βAPP). However, whether melatonin can directly regulate the βAPP-cleaving proteases ('secretases') has not been investigated so far. In this study, we establish that melatonin stimulates the α-secretase cleavage of βAPP in cultured neuronal and non-neuronal cells. This effect is fully reversed by ADAM10- and ADAM17-specific inhibitors and requires both plasma membrane-located melatonin receptor activation, and ERK1/2 phosphorylation. Moreover, we demonstrate that melatonin upregulates both ADAM10 and ADAM17 catalytic activities and endogenous protein levels. Importantly, genetic depletion of one or the other protease in mouse embryonic fibroblasts prevents melatonin stimulating constitutive and PKC-regulated sAPPα secretion and ADAM10/ADAM17 catalytic activities. Furthermore, we show that melatonin induces ADAM10 and ADAM17 promoter transactivation, and we identify the targeted promoter regions. Finally, we correlate melatonin-dependent sAPPα production with a protection against staurosporine-induced apoptosis. Altogether, our results provide the first demonstration that melatonin upregulates the nonamyloidogenic ADAM10 and ADAM17 proteases through melatonin receptor activation, ERK phosphorylation and the transactivation of some specific regions of their promoters and further underline the preventive rather than curative nature of melatonin regarding AD treatment.