Neuroprotection with the Endozepine Octadecaneuropeptide, ODN

Title:Neuroprotection with the Endozepine Octadecaneuropeptide, ODN

Volume: 24 Issue: 33

Author(s): Olfa Masmoudi-Kouki*, Yosra Hamdi, Ikram Ghouili, Seyma Bahdoudi, Hadhémi Kaddour, Jérôme Leprince, Hélène Castel, Hubert Vaudry, Mohamed Amri, David Vaudry and Marie-Christine Tonon

Affiliation:

• University Tunis El Manar, Faculty of Science of Tunis, LR18ES03 Laboratory Neurophysiology, Cellular Physiopathology and Biomolecules valorization, 2092 Tunis,Tunisia

Keywords: Endozepines, ODN, astroglial cells, oxidative injuries, apoptosis, glioprotection, neuroprotection.

Abstract: 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.

Cite this article as:

Masmoudi-Kouki Olfa *, Hamdi Yosra , Ghouili Ikram , Bahdoudi Seyma , Kaddour Hadhémi , Leprince Jérôme , Castel Hélène , Vaudry Hubert , Amri Mohamed , Vaudry David and Tonon Marie-Christine , Neuroprotection with the Endozepine Octadecaneuropeptide, ODN, Current Pharmaceutical Design 2018; 24 (33) . https://dx.doi.org/10.2174/1381612824666181112111746