Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Neurosteroid Dehydroepiandrosterone Interacts with Nerve Growth Factor (NGF) Receptors, Preventing Neuronal Apoptosis
Δημιουργός/Συγγραφέας:	Lazaridis, Iakovos Charalampopoulos, Ioannis Alexaki, Vassilia-Ismini Avlonitis, Nicolaos Pediaditakis, Iosif Efstathopoulos, Paschalis [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora Castanas, Elias Gravanis, Achille
Εκδότης:	Public Library Science
Τόπος έκδοσης:	San Francisco
Ημερομηνία:	2011-04
Γλώσσα:	Αγγλικά
ISSN:	1544-9173
DOI:	10.1371/journal.pbio.1001051
Περίληψη:	The neurosteroid dehydroepiandrosterone (DHEA), produced by neurons and glia, affects multiple processes in the brain, including neuronal survival and neurogenesis during development and in aging. We provide evidence that DHEA interacts with pro-survival TrkA and pro-death p75(NTR) membrane receptors of neurotrophin nerve growth factor (NGF), acting as a neurotrophic factor: (1) the anti-apoptotic effects of DHEA were reversed by siRNA against TrkA or by a specific TrkA inhibitor; (2) [(3)H]-DHEA binding assays showed that it bound to membranes isolated from HEK293 cells transfected with the cDNAs of TrkA and p75(NTR) receptors (K(D): 7.4 +/- 1.75 nM and 5.6 +/- 0.55 nM, respectively); (3) immobilized DHEA pulled down recombinant and naturally expressed TrkA and p75(NTR) receptors; (4) DHEA induced TrkA phosphorylation and NGF receptor-mediated signaling; Shc, Akt, and ERK1/2 kinases down-stream to TrkA receptors and TRAF6, RIP2, and RhoGDI interactors of p75(NTR) receptors; and (5) DHEA rescued from apoptosis TrkA receptor positive sensory neurons of dorsal root ganglia in NGF null embryos and compensated NGF in rescuing from apoptosis NGF receptor positive sympathetic neurons of embryonic superior cervical ganglia. Phylogenetic findings on the evolution of neurotrophins, their receptors, and CYP17, the enzyme responsible for DHEA biosynthesis, combined with our data support the hypothesis that DHEA served as a phylogenetically ancient neurotrophic factor.
Τίτλος πηγής δημοσίευσης:	Plos Biology
Τόμος/Κεφάλαιο:	9
Τεύχος:	4
Σελίδες:	[14]
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General)
Λέξεις-Κλειδιά:	Life Sciences & Biomedicine - Other Topics
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Όροι και προϋποθέσεις δικαιωμάτων:	This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Ηλεκτρονική διεύθυνση περιοδικού (link) :	http://search.ebscohost.com/direct.asp?db=ofs&jid=%22RXN%22&scope=site
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Οργανικής και Φαρμακευτικής Χημείας (ΙΟΦΧ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο