Dejda, Agnieszka; Seaborn, Tommy; Bourgault, Steve; Touzani, Omar; Fournier, Alain; Vaudry, Hubert et Vaudry, David (2012). PACAP and a novel stable analogue protect rat brain from ischemia through same mechanisms In: 10th International Symposium on VIP-PACAP and Related Peptides, December 13-16, 2011, Eilat, ISRAEL.
Ce document n'est pas hébergé sur EspaceINRS.Résumé
PACAP exerts protective activities in numerous models of
neurological disorders involving neurodegeneration. However, the use of PACAP as a clinically efficient drug might
be limited due to its poor metabolic stability and adverse
physiological effects. By combining identification of enzymatic cleavage sites with targeted chemical modifications, a
metabolically stable and potent PACAP38 analogue, acetyl-
[Ala15, Ala20]PACAP38-propylamide, was recently developed. The in vivo biological activity of this new compound
was evaluated and compared to the native peptide using a rat
model of middle cerebral artery occlusion (MCAO). The
results show that PACAP38 and its analogue, administered
intravenously, strongly reduce the infarct volume and improve
neurological impairment induced by stroke. Investigation of
the mechanisms involved indicates that the 2 peptides act
through same mechanisms. In particular, they inhibit the
expression of Bad, caspase 3, MIP-1α, Nos2, TNF-α and NFκB mRNAs, and increase ERK2, Bcl-2 and IL-6 mRNA
levels. These results indicate that the neuroprotective effect of
PACAP, after MCAO, is not only due to its ability to inhibit
apoptosis but also to modulate the inflammatory response.
Altogether, the present study highlights the potential therapeutic efficacy of very low concentrations of PACAP or its
metabolically stable derivative for the treatment of stroke.
This work is supported by INSERM, TC2N Interreg
Project, LARC-Neurosciences Network and the Region of
Haute-Normandie.
| Type de document: | Document issu d'une conférence ou d'un atelier |
|---|---|
| Informations complémentaires: | Affiche scientifique Journal of Molecular Neuroscience 48(suppl. 1):S8-S159 |
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 28 janv. 2024 14:55 |
| Dernière modification: | 28 janv. 2024 14:55 |
| URI: | https://espace.inrs.ca/id/eprint/14119 |
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