Neuroprotection with the Endozepine Octadecaneuropeptide, ODN
| Autor: | Marie-Christine Tonon, Yosra Hamdi, Jérôme Leprince, Olfa Masmoudi-Kouki, Hubert Vaudry, Ikram Ghouili, Hadhemi Kaddour, Hélène Castel, Seyma Bahdoudi, Mohamed Amri, David Vaudry |
|---|---|
| Přispěvatelé: | Université de Tunis El Manar (UTM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie (PRIMACEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis (FST) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
MAPK/ERK pathway
Endozepine [SDV]Life Sciences [q-bio] Neuroprotection Apoptosis [SDV.BC]Life Sciences [q-bio]/Cellular Biology 01 natural sciences Oxidative injuries Endozepines 03 medical and health sciences chemistry.chemical_compound ODN Drug Discovery medicine Animals Humans Astroglial cells Receptor Protein kinase C 030304 developmental biology Pharmacology Diazepam Binding Inhibitor Neurons 0303 health sciences Neurodegeneration Neuropeptides hemic and immune systems respiratory system medicine.disease Peptide Fragments 0104 chemical sciences Cell biology 010404 medicinal & biomolecular chemistry Metabotropic receptor medicine.anatomical_structure Neuroprotective Agents chemistry Brain Injuries Glioprotection Astrocyte |
| Zdroj: | Current Pharmaceutical Design Current Pharmaceutical Design, Bentham Science Publishers, 2018, 24 (33), pp.3918-3925. ⟨10.2174/1381612824666181112111746⟩ |
| ISSN: | 1381-6128 |
| Popis: | International audience; The term endozepines designates a family of astroglia-secreted proteins including the diazepambinding inhibitor (DBI) and its processing products, which have been originally isolated and characterized as endogenous ligands of benzodiazepine receptors. It is now clearly established that the octadecaneuropeptide ODN (DBI33-50), acting through the central-type benzodiazepine receptor or a metabotropic receptor, exerts important functions such as proconflict behavior, induction of anxiety, inhibition of pentobarbital-provoked sleep, decrease of water consumption and reduction of food intake. To mediate its effects, ODN regulates both glial cell and neuronal activities by acting on neurosteroid biosynthesis and/or neuropeptide expression. In addition, ODN stimulates astrocyte proliferation and protects both neurons and astrocytes from oxidative stress-induced cell death. The antiapoptotic effect of ODN on neural cells is mediated through activation of the ODN metabotropic receptor positively coupled to PKA, PKC and MAPK/ERK transduction pathways, which ultimately reduces the pro-apoptotic gene Bax and stimulates Bcl-2 expressions, and inhibits intracellular reactive oxygen species accumulation. The imbalance in favor of Bcl2 promotes mitochondria functions and blocks in turn caspases activation while at the same time, ODN also activates the endogenous antioxidant system i.e. glutathione biosynthesis, and expression and activities of antioxidant enzymes. In cultured astrocytes, DBI expression is up-regulated during moderate oxidative stress, and authentic ODN production is increased, suggesting that ODN may act as a paracrine factor protecting neighboring neurons. Taken together, the remarkable effect of ODN on the apoptotic cascade suggests that innovative ODN derivatives could potentially be useful for treatment of cerebral injuries involving oxidative stress and neurodegeneration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|