Amyloid-ß induced toxicity involves ganglioside expression and is sensitive to GM1 neuroprotective action.
Neurochem Int
; 59(5): 648-55, 2011 Oct.
Article
en En
| MEDLINE
| ID: mdl-21723896
The effect of Aß25-35 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 Aß25-35 affected ganglioside expression, depending on the peptide aggregation state, that is, fibrillar Aß25-35 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 Aß25-35, 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 Aß-induced alterations on GSK3ß dephosphorylation/activation state. Results demonstrated an important effect after 24-h incubation, with GM1 preventing the Aß-induced dephosphorylation (activation) of GSK3ß, 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 Aß-induced toxicity. This may be useful for designing new therapeutic strategies for Alzheimer's treatment.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
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Péptidos beta-Amiloides
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Fármacos Neuroprotectores
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Gangliósido G(M1)
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Gangliósidos
Tipo de estudio:
Diagnostic_studies
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Guideline
Límite:
Animals
Idioma:
En
Revista:
Neurochem Int
Año:
2011
Tipo del documento:
Article
País de afiliación:
Brasil