Longpré, Fanny; Garneau, Philippe; Christen, Yves et Ramassamy, Charles 
ORCID: https://orcid.org/0000-0002-3252-5878
(2006).
Protection by EGb 761 against beta-amyloid-induced neurotoxicity: Involvement of NF-kappa B, SIRT1, and MAPKs pathways and inhibition of amyloid fibril formation
Free Radical Biology and Medicine
, vol. 41
, nº 12.
pp. 1781-1794.
DOI: 10.1016/j.freeradbiomed.2006.08.015.
Résumé
A peptide-induced toxicity is mediated through oxidative stress and is associated with an activation of intracellular signaling such as the redox-sensitive transcription factor NF-kappa B and MAPK pathways. We demonstrate on neuroblastoma cell line N2a that EGb 761 could prevent the activation of NF-kappa B, ERK1/2, and JNK pathways induced by A beta. Furthermore, our results show that EGb 761 can also activate SIRT1. This activation could explain the reduction of NF-kB activity by promoting the deacetylation of Lys310 of subunit p65. On the other hand, aggregation of A beta to insoluble fibrils is a crucial step in A beta-induced neurotoxicity. Using fluorescence spectroscopy with thioflavin T and electron microscopy, we demonstrate that EGb 761 and its flavonoid fraction (CP 205) could prevent the A beta fibril (fA beta) formation in vitro. Finally we show that A beta is less toxic to N2a neuroblastoma cells when the peptide is previously incubated with the flavonoid fraction or EGb 761 during the fibril formation period. On the other hand, the ginkgolide compound BN 52021 was not able to prevent fA beta formation. Interestingly it could also protect cells against A beta toxicity. Our study demonstrates that the protection of neuronal cells by EGb 761 against A beta could involve different mechanisms as the regulation of several key intracellular pathways and the inhibition of fA beta formation and implicate more than its free radical scavenging property.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | Antioxidants; Ginkgolides; Flavonoids; Alzheimer's disease; NF-kB; MAPKs |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 04 nov. 2024 20:33 |
| Dernière modification: | 04 nov. 2024 20:33 |
| URI: | https://espace.inrs.ca/id/eprint/14917 |
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