Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	BNN27, a 17-spiroepoxy steroid derivative, interacts with and activates p75 neurotrophin receptor, rescuing cerebellar granule neurons from apoptosis
Δημιουργός/Συγγραφέας:	Pediaditakis I. Kourgiantaki A. [EL] Προύσης, Κυριάκος[EN] Prousis, Kyriakos Potamitis C. Xanthopoulos K.P. [EL] Ζερβού, Μαρία[EN] Zervou, Maria [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora Charalampopoulos I. Gravanis A.
Εκδότης:	Frontiers Media S.A.
Ημερομηνία:	2016
Γλώσσα:	Αγγλικά
ISSN:	1663-9812
DOI:	10.3389/fphar.2016.00512
Περίληψη:	Neurotrophin receptors mediate a plethora of signals affecting neuronal survival. The p75 pan-neurotrophin receptor controls neuronal cell fate after its selective activation by immature and mature isoforms of all neurotrophins. It also exerts pleiotropic effects interacting with a variety of ligands in different neuronal or non-neuronal cells. In the present study, we explored the biophysical and functional interactions of a blood-brain-barrier (BBB) permeable, C17-spiroepoxy steroid derivative, BNN27, with p75NTR receptor. BNN27 was recently shown to bind to NGF high-affinity receptor, TrkA. We now tested the p75NTR-mediated effects of BNN27 in mouse Cerebellar Granule Neurons (CGNs), expressing p75NTR, but not TrkA receptors. Our findings show that BNN27 physically interacts with p75NTR receptors in specific amino-residues of its extracellular domain, inducing the recruitment of p75NTR receptor to its effector protein RIP2 and the simultaneous release of RhoGDI in primary neuronal cells. Activation of the p75NTR receptor by BNN27 reverses serum deprivation-induced apoptosis of CGNs resulting in the decrease of the phosphorylation of pro-apoptotic JNK kinase and of the cleavage of Caspase-3, effects completely abolished in CGNs, isolated from p75NTR null mice. In conclusion, BNN27 represents a lead molecule for the development of novel p75NTR ligands, controlling specific p75NTR-mediated signaling of neuronal cell fate, with potential applications in therapeutics of neurodegenerative diseases and brain trauma.
Τίτλος πηγής δημοσίευσης:	Frontiers in Pharmacology
Τόμος/Κεφάλαιο:	7
Τεύχος:	DEC
Θεματική Κατηγορία:	[EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	DHEA Molecular dynamics Nerve growth factor (NGF) Neuronal apoptosis Neurotrophin receptors signaling P75 neurotrophin receptor STD NMR Steroid
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2016 Pediaditakis, Kourgiantaki, Prousis, Potamitis, Xanthopoulos, Zervou, Calogeropoulou, Charalampopoulos and Gravanis.
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Gold, Green
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο