Dépôt numérique

Characterization of the neurotrophic effects of PACAP and development of new analogs for therapeutic applications

Vaudry, David; Doan, Ngoc Duc; Chatenet, David ORCID logoORCID: 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.

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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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