title: Amyloid-β induced toxicity involves ganglioside expression and is sensitive to GM1 neuroprotective action.
abstract: The effect of Aβ25-35 peptide, in its fibrillar and non-fibrillar forms, on ganglioside expression in organotypic hippocampal slice cultures was investigated. Gangliosides were endogenously labeled with D-[1-C(14)] galactose and results showed that Aβ25-35 affected ganglioside expression, depending on the peptide aggregation state, that is, fibrillar Aβ25-35 caused an increase in GM3 labeling and a reduction in GD1b labeling, whereas the non-fibrillar form was able to enhance GM1 expression. Interestingly, GM1 exhibited a neuroprotective effect in this organotypic model, since pre-treatment of the hippocampal slices with GM1 10 μM was able to prevent the toxicity triggered by the fibrillar Aβ25-35, when measured by propidium iodide uptake protocol. With the purpose of further investigating a possible mechanism of action, we analyzed the effect of GM1 treatment (1, 6, 12 and 24h) upon the Aβ-induced alterations on GSK3β dephosphorylation/activation state. Results demonstrated an important effect after 24-h incubation, with GM1 preventing the Aβ-induced dephosphorylation (activation) of GSK3β, a signaling pathway involved in apoptosis triggering and neuronal death in models of Alzheimer's disease. Taken together, present results provide a new and important support for ganglioside participation in development of Alzheimer's disease experimental models and suggest a protective role for GM1 in Aβ-induced toxicity. This may be useful for designing new therapeutic strategies for Alzheimer's treatment.
authors: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, ICBS, UFRGS, Brazil.
authors: Fernando
authors: F
authors: Kreutz
authors: Rudimar L
authors: RL
authors: Frozza
authors: Ana Carolina
authors: AC
authors: Breier
authors: Valeska A
authors: VA
authors: de Oliveira
authors: Ana Paula
authors: AP
authors: Horn
authors: Letícia F
authors: LF
authors: Pettenuzzo
authors: Carlos Alexandre
authors: CA
authors: Netto
authors: Christianne Gazzana
authors: CG
authors: Salbego
authors: Vera Maria Treis
authors: VM
authors: Trindade
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002855:Chromatography, Thin Layer; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005732:Gangliosides / Q000096:biosynthesis*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009454:Neurofibrils / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D005732:Gangliosides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D005677:G(M1) Ganglioside; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3