Amyloid-β induced toxicity involves ganglioside expression and is sensitive to GM1 neuroprotective action

• DOI: 10.1016/j.neuint.2011.06.007
• Publication Date: 2011-06-27T21:27:57Z
• Authors: Fernando Kreutz; Rudimar L. Frozza; Ana Carolina Breier; Valeska A. de Oli...; Ana Paula Horn; Letícia F. Petten...; Carlos Alexandre ...; Christianne Gazza...; Vera Maria Treis ...
• Keywords: Dephosphorylation; Ganglioside; Neurotoxicity

The effect of Aβ25-35 peptide, in its fibrillar and non-fibrillar forms, on ganglioside expression organotypic hippocampal slice cultures was investigated. Gangliosides were endogenously labeled with D-[1-C(14)] galactose results showed that affected expression, depending the peptide aggregation state, is, caused an increase GM3 labeling a reduction GD1b labeling, whereas form able to enhance GM1 expression. Interestingly, exhibited neuroprotective this model, since pre-treatment slices 10 μM prevent toxicity triggered by Aβ25-35, when measured propidium iodide uptake protocol. With purpose further investigating possible mechanism action, we analyzed treatment (1, 6, 12 24h) upon Aβ-induced alterations GSK3β dephosphorylation/activation state. Results demonstrated important after 24-h incubation, preventing dephosphorylation (activation) GSK3β, signaling pathway involved apoptosis triggering neuronal death models Alzheimer's disease. Taken together, present provide new support for participation development disease experimental suggest protective role toxicity. This may be useful designing therapeutic strategies treatment.