Vaudry, David; Doan, Ngoc Duc; Chatenet, David 
ORCID: https://orcid.org/0000-0002-7270-4328; Bourgault, Steve; Dejda, Agnieszka; Basille, Magali; Botia, Béatrice; Vaudry, Hubert et Fournier, Alain
(2012).
Characterization of the neurotrophic effects of PACAP and development of new analogs for therapeutic applications
In: Summer Neuropeptide Conference / Meeting of the European-Neuropeptide-Club (ENC), May 22-25, 2011, Boston, MA.
Résumé
Pituitary adenylate cyclase-activating polypeptide (PACAP)
is a 38-amino acid C-terminally α-amidated peptide that was
first isolated from ovine hypothalamic extracts on the basis of
its ability to stimulate adenylyl cyclase from rat anterior
pituitary cells. The wide distribution of PACAP and its receptors in the central nervous system (CNS) and in peripheral
tissues suggested that the peptide could be involved in a large
array of biological activities. Indeed, PACAP exerts numerous
effects on the cardiovascular and immune systems, the urogenital and respiratory tracts, the endocrine glands, the gonads
and the CNS [1]. In particular, during brain development,
PACAP regulates proliferation, migration, differentiation and
survival of neural cells. In the adult brain, PACAP has beneficial effects in various pathological states including Parkinson’s disease, ischemia and traumatic brain injury [2]. These
results suggest that PACAP could have therapeutic value for
the treatment of several pathological states. However, PACAP
is prone to rapid enzymatic degradation, which could preclude
its use as a therapeutic agent. In particular, it has been shown
that after an intravenous injection, PACAP is rapidly metabolized by dipeptidyl peptidase IV (DPP IV), which leads to the
formation of PACAP(3–38) and PACAP(5–38). This conversion of the active peptide into antagonists may compromise therapeutic applications. Furthermore PACAP acts on 3 different receptors which can induce some side effects. These
observations prompted us to develop PACAP analogs with
higher stability and specificity. All analogs were tested
for their ability to bind PACAP receptors, to induce
calcium mobilization and to promote cell differentiation
or survival in vitro. Some of the analogs are now being
tested in vivo and the mechanisms involved in their
effects are investigated.
Supported by INSERM (U982), INRS, IREB, Interreg 4A
TC2N project and Conseil Régional de Haute-Normandie.
[1] Vaudry D., Falluel-Morel A., Bourgault S., Basille M.,
Burel D., Wurtz O., Fournier A. Chow B.K.C., Hashimoto
H., Vaudry H. Pituitary adenylate cyclase-activating
polypeptide and its receptors: 20 years after the discovery.
Pharm. Rev. 2009, 61: 283–357.
[2] Seaborn T, Masmoudi-Kouli O, Fournier A, Vaudry H,
Vaudry D. Protective Effects of Pituitary Adenylate
Cyclase-Activating Polypeptide (PACAP) Against Apoptosis. Curr Pharm Des. 2011, 17: 204–214.
| Type de document: | Document issu d'une conférence ou d'un atelier |
|---|---|
| Informations complémentaires: | Présentation orale Journal of Molecular Neuroscience 48(suppl. 1):S182-S183 |
| Mots-clés libres: | Cyclase; Activating; Polypeptide |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 28 janv. 2024 14:57 |
| Dernière modification: | 28 janv. 2024 14:57 |
| URI: | https://espace.inrs.ca/id/eprint/14136 |
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