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P2‐219: identification of enzymes involved in n‐terminal truncation and modification of amyloid peptide
Author(s) -
Caillava Celine,
Sevalle Jean,
Checler Frederic
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1101
Subject(s) - exopeptidase , aminopeptidase , peptide , biology , enzyme , biochemistry , amyloid (mycology) , microbiology and biotechnology , amino acid , leucine , botany
Methods: For this purpose, organotypic hippocampal cultures (OHCs) were exposed to Aß1-42 (2 mM) for 48 hours with or without curcumin (0.5, 1, 5 and 10 mM). We also analysed the effect of LY294002 (5 mM), an inhibitor of phosphoinositide-3-kinase (PI3-K) pathway in OHCs exposed to Aß1-42 (2 mM) and curcumin (10 mM). Cell death was measured by propidium iodide uptake in the slices and some cell signaling pathways were investigated by performing Western blot assay with specifics antibodies. Moreover, we measured the synaptophysin expression, involved in the regulation of synaptic plasticity, by Western blot assay. Results:Our results show that Aß1-42 peptide caused about 30% of cell damage in hippocampal slices, a significant increase when compared to controls cultures. The treatment with 5 and 10 mM of curcumin decreased the cell death significantly. The curcumin treatment prevented the decreased in synaptophysin expression after exposure to Aß peptide. Aß1-42 neurotoxicity resulted in an increased in phosphorylated (Ser45) ß-catenin and a decreased in ß-catenin immunocontent and the curcumin treatment prevented this ß-catenin destabilization. Additionally, the curcumin (10 mM) neuroprotection was prevented by LY294002. Immunoblotting revealed that curcumin induced the phosphorylation/activation of Akt and the phosphorylation/inactivation of glycogen synthase kinase-3ß (GSK-3ß). Conclusions: These results reinforce the neuroprotective effect of curcumin and add some evidence that its mechanism may involve the PI3-K pathway and ß-catenin signaling, a key transducer of the Wnt signaling pathway. We also provide interesting perspectives on the use of our model in the study of this disease process.