Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis.

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 receptor...

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Autores principales:	Iakovos Lazaridis, Ioannis Charalampopoulos, Vassilia-Ismini Alexaki, Nicolaos Avlonitis, Iosif Pediaditakis, Paschalis Efstathopoulos, Theodora Calogeropoulou, Elias Castanas, Achille Gravanis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/dbe163e54a0e4535ad2d6f966129287a
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spelling	oai:doaj.org-article:dbe163e54a0e4535ad2d6f966129287a2021-11-18T05:36:13ZNeurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis.1544-91731545-788510.1371/journal.pbio.1001051https://doaj.org/article/dbe163e54a0e4535ad2d6f966129287a2011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21541365/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The 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.Iakovos LazaridisIoannis CharalampopoulosVassilia-Ismini AlexakiNicolaos AvlonitisIosif PediaditakisPaschalis EfstathopoulosTheodora CalogeropoulouElias CastanasAchille GravanisPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 9, Iss 4, p e1001051 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Iakovos Lazaridis Ioannis Charalampopoulos Vassilia-Ismini Alexaki Nicolaos Avlonitis Iosif Pediaditakis Paschalis Efstathopoulos Theodora Calogeropoulou Elias Castanas Achille Gravanis Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis.
description	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.
format	article
author	Iakovos Lazaridis Ioannis Charalampopoulos Vassilia-Ismini Alexaki Nicolaos Avlonitis Iosif Pediaditakis Paschalis Efstathopoulos Theodora Calogeropoulou Elias Castanas Achille Gravanis
author_facet	Iakovos Lazaridis Ioannis Charalampopoulos Vassilia-Ismini Alexaki Nicolaos Avlonitis Iosif Pediaditakis Paschalis Efstathopoulos Theodora Calogeropoulou Elias Castanas Achille Gravanis
author_sort	Iakovos Lazaridis
title	Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis.
title_short	Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis.
title_full	Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis.
title_fullStr	Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis.
title_full_unstemmed	Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis.
title_sort	neurosteroid dehydroepiandrosterone interacts with nerve growth factor (ngf) receptors, preventing neuronal apoptosis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/dbe163e54a0e4535ad2d6f966129287a
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Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis.

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