Το ερευνητικό μας ενδιαφέρον επικεντρώνεται στην μελέτη των μοριακών μηχανισμών που εκκινούν οι αυξητικοί παράγοντες και οι υποδοχείς τους για να ρυθμίσουν την αναγεννητική ικανότητα του ενήλικου νευρικού συστήματος. Τέτοια μόρια, όπως οι Νευροτροφίνες, ελέγχουν την ανάπτυξη και συντήρηση του εγκεφάλου κατά την ενηλικίωση και τη γήρανση, ενώ συμμετέχουν σημαντικά στην επιβίωση, τη διαφοροποίηση και την επιδιόρθωση των νευρώνων. Οι μελέτες μας εστιάζουν σε πειράματα δομής-λειτουργίας των υποδοχέων νευροτροφινών καθώς και στη φαρμακολογική ανάπτυξη νέων προσδεμάτων για αυτούς τους υποδοχείς με νευρογενείς και αναγεννητικές ιδιότητες. Στόχος της εργασίας μας είναι να προσδιορίσουμε και να αποκρυπτογραφήσουμε τις πολλαπλές οδούς σηματοδότησης των υποδοχέων νευροτροφινών στην νευρογένεση του ενήλικου εγκεφάλου (χρησιμοποιώντας κατάλληλα ζωϊκά μοντέλα και τρισδιάστατες καλλιέργειες νευρικών βλαστικών κυττάρων) κι επομένως να ενισχύσουμε την ικανότητά τους να προάγουν την αναγέννηση του νευρικού ιστού, με στόχο τη βελτιστοποίηση του θεραπευτικού τους δυναμικού σε ζωϊκά μοντέλα νευροεκφυλιστικών νόσων (Νόσος Αλτζχάιμερ και τραυματισμός νωτιαίου μυελού).
Efstathopoulos P, Kourgiantaki A, Karali K, Sidiropoulou K, Margioris AN, Gravanis A, Charalampopoulos I. (2015) Fingolimod induces neurogenesis in adult mouse hippocampus and improves contextual fear memory. Transl Psychiatry 5:e685.
Charalampopoulos I, Vicario A, Pediaditakis I, Gravanis A, Simi A, Ibanez CF. (2012) Genetic Dissection of Neurotrophin Signaling through the p75 Neurotrophin Receptor. Cell Rep. 2:1563-70.
Lazaridis I, Charalampopoulos I, Alexaki VI, Avlonitis N, Pediaditakis I, Efstathopoulos P, Calogeropoulou T, Castanas E, Gravanis A. (2011) Neurosteroids bind with high affinity and activate Nerve Growth Factor (NGF) receptors, preventing neuronal apoptosis. PloS Biol. 9: e1001051.
Vilar M, Charalampopoulos I, Kenchappa RS, Simi A, Karaca E, Reversi A, Choi S, Bothwell M, Mingarro I, Friedman WJ, Schiavo G, Bastiaens PI, Verveer PJ, Carter BD, Ibanez CF. (2009) Activation of the p75 neurotrophin receptor through conformational rearrangement of disulphide-linked receptor dimmers. Neuron 62: 72-83.
Charalampopoulos I, Tsatsanis C, Dermitzaki E, Alexaki VI, Castanas E, Margioris AN, Gravanis A. (2004) Dehydroepiandrosterone and allopregnanolone protect sympathoadrenal medulla cells against apoptosis via antiapoptotic Bcl-2 proteins. Proc Natl Acad Sci U S A. 101:8209-14.
Ibán-Arias R, Lisa S, Mastrodimou N, Kokona D, Koulakis E, Iordanidou P, Kouvarakis A, Fothiadaki M, Papadogkonaki S, Sotiriou A, Katerinopoulos HE, Gravanis A, Charalampopoulos I, Thermos K. The Synthetic Microneurotrophin BNN27 Affects Retinal Function in Rats With Streptozotocin-Induced Diabetes. Diabetes. 2018 Feb;67(2):321-333.
Alexaki VI, Fodelianaki G, Neuwirth A, Mund C, Kourgiantaki A, Ieronimaki E, Lyroni K, Troullinaki M, Fujii C, Kanczkowski W, Ziogas A, Peitzsch M, Grossklaus S, Sönnichsen B, Gravanis A, Bornstein SR, Charalampopoulos I, Tsatsanis C, Chavakis T. DHEA inhibits acute microglia-mediated inflammation through activation of the TrkA-Akt1/2-CREB-Jmjd3 pathway. Mol Psychiatry. 2017 Sep 12.
Bonetto G, Charampopoulos I, Gravanis A, Karagogeos D. The novel synthetic microneurotrophin BNN27 protects mature oligodendrocytes against cuprizone-induced death, through the NGF receptor TrkA. Glia, 2017, Aug;65(8):1376-1394.
Botsakis K, Mourtzi T, Panagiotakopoulou V, Vreka M, Stathopoulos G, Pediaditakis I, Charalampopoulos I, Gravanis A, Delis F, Antoniou K, Zisimopoulos D, Georgiou C, Panagopoulos N, Matsokis N, Angelatou F. BNN20, a synthetic microneurotrophin, strongly protects dopaminergic neurons in the "Weaver" mouse, a genetic model of dopamine-denervation, acting through the TrkB neurotrophin receptor. Neuropharmacology, 2017, Apr 28;121:140-157.
Gravanis A, Pediaditakis I, Charalampopoulos I. Synthetic microneurotrophins in therapeutics of neurodegeneration. Oncotarget, 2017, Feb 7;8(6):9005-9006.
Pediaditakis I, Kourgiantaki A, Prousis KC, Potamitis C, Xanthopoulos KP, Zervou M, Calogeropoulou T, Charalampopoulos I#, Gravanis A. BNN27, a 17-Spiroepoxy Steroid Derivative, Interacts With and Activates p75 Neurotrophin Receptor, Rescuing Cerebellar Granule Neurons from Apoptosis. Front Pharmacol. 2016 Dec 26;7:512 (# Corresponding author)
Pediaditakis I, Efstathopoulos P, Prousis KC, Zervou M, Arévalo JC, Alexaki VI, Nikoletopoulou V, Karagianni E, Potamitis C, Tavernarakis N, Chavakis T, Margioris AN, Venihaki M, Calogeropoulou T, Charalampopoulos I#, Gravanis A. Selective and differential interactions of BNN27, a novel C17-spiroepoxy steroid derivative, with TrkA receptors, regulating neuronal survival and differentiation. Neuropharmacology, 2016 Dec;111:266-282 (# Corresponding author)
Vazgiouraki E, Papadakis VM, Efstathopoulos P, Lazaridis I, Charalampopoulos I, Fotakis C, Gravanis A. Application of multispectral imaging detects areas with neuronal myelin loss, without tissue labelling. Microscopy (Oxf), 2016 Apr;65(2):109-18
Efstathopoulos P, Kourgiantaki A, Karali K, Sidiropoulou K, Margioris AN, Gravanis A, Charalampopoulos I#. Fingolimod induces neurogenesis in adult mouse hippocampus and improves contextual fear memory. Transl Psychiatr,. 2015 Nov 24;5:e685. (# Corresponding author)
Simitzi C, Efstathopoulos P, Kourgiantaki A, Ranella A, Charalampopoulos I, Fotakis C, Αthanassakis Ι, Stratakis E, Gravanis A. Data in support on the shape of Schwann cells and sympathetic neurons onto microconically structured silicon surfaces. Data Brief, 2015 Jul 31;4:636-40.
Simitzi C, Efstathopoulos P, Kourgiantaki A, Ranella A, Charalampopoulos I, Fotakis C, Athanassakis I, Stratakis E, Gravanis A. Laser fabricated discontinuous anisotropic microconical substrates as a new model scaffold to control the directionality of neuronal network outgrowth. Biomaterials, 2015 Oct;67:115-28
Lisa S, Iban-Arias R, Kokona D, Charalampopoulos I, Gravanis A, Thermos K. Effects of novel synthetic microneurotrophins in diabetic retinopathy. Springerplus. 2015 Jun 12;4(Suppl 1):L25.
Pediaditakis I, Iliopoulos I, Theologidis I, Delivanoglou N, Margioris AN, Charalampopoulos I#, Gravanis A. Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors. Endocrinology, 2015 Jan;156(1):16-23. (# Corresponding author)
Anagnostopoulou V, Pediaditakis I, Alkahtani S, Schmidt E.M, Lang F, Gravanis A, Charalampopoulos I#, Stournaras C. Differential effects of Dehydroepiandrosterone and Testosterone in prostate and colon cancer cell apoptosis: the role of Nerve Growth Factor (NGF) receptors. Endocrinology, 2013, 154(7):2446-56. (# Corresponding author)
Charalampopoulos I, Vicario A, Pediaditakis I, Gravanis A, Simi A, Ibáñez CF. Genetic Dissection of Neurotrophin Signaling through the p75 Neurotrophin Receptor. Cell Rep., 2012 Dec 27;2(6):1563-70
Notas G, Alexaki VI, Kampa M, Pelekanou V, Charalampopoulos I, Sabour-Alaoui S, Pediaditakis I, Dessirier V, Gravanis A, Stathopoulos EN, Tsapis A, Castanas E. APRIL binding to BCMA activates a JNK2-FOXO3-GADD45 pathway and induces a G2/M cell growth arrest in liver cells. J Immunol. 2012 Nov 15;189(10):4748-58. doi: 10.4049/jimmunol.1102891.
Kokona D, Mastrodimou N, Pediaditakis I, Charalampopoulos I, Schmid HA, Thermos K. Pasireotide (SOM230) protects the retina in animal models of ischemia induced retinopathies. Exp Eye Res. 2012 Oct;103:90-8.
Kokona D, Charalampopoulos I, Pediaditakis I, Gravanis A, Thermos K. The neurosteroid dehydroepiandrosterone (DHEA) protects the retina from AMPA-induced excitotoxicity: NGF TrkA receptor involvement. Neuropharmacology. 2012 Apr;62(5-6):2106-17.
Gravanis A, Calogeropoulou T, Panoutsakopoulou V, Thermos K, Neophytou C, Charalampopoulos I. Neurosteroids and microneurotrophins signal through NGF receptors to induce prosurvival signaling in neuronal cells. Sci Signal. 2012 Oct 16;5(246)
Kampa M, Pelekanou V, Gallo D, Notas G, Troullinaki M, Pediaditakis I, Charalampopoulos I, Jacquot Y, Leclercq G, Castanas E. ERα17p, an ERα P295 -T311 fragment, modifies the migration of breast cancer cells, through actin cytoskeleton rearrangements. J Cell Biochem. 2011 Dec;112(12):3786-96.
Lazaridis I.*, Charalampopoulos I*, Alexaki VI, Avlonitis N, Pediaditakis I, Efstathopoulos P, Calogeropoulou T, Castanas E, Gravanis A. Neurosteroids bind with high affinity and activate Nerve Growth Factor (NGF) receptors, preventing neuronal apoptosis. PloS Biol., Vol 9(4), April 2011, (*equal contributors)
Fragkouli A, Tzinia AK, Charalampopoulos I, Gravanis A, Tsilibary EC. Matrix metalloproteinase-9 participates in NGF-induced α-secretase cleavage of amyloid-β protein precursor in PC12 cells. J Alzheimers Dis. 2011;24(4):705-19.
Calogeropoulou T, Avlonitis N*, Minas V*, Alexi X, Pantzou A, Charalampopoulos I, Zervou M, Vergou V, Katsanou ES, Lazaridis I, Alexis MN, Gravanis A. Novel dehydroepiandrosterone derivatives with antiapoptotic, neuroprotective activity. J Med Chem. 2009 Nov 12;52(21):6569-87.
Vilar M, Charalampopoulos I, Kenchappa RS, Reversi A, Klos-Applequist JM, Karaca E, Simi A, Spuch C, Choi S, Friedman WJ, Ericson J, Schiavo G, Carter BD, Ibáñez CF. Ligand-independent signaling by disulfide-crosslinked dimers of the p75 neurotrophin receptor. J Cell Sci. 2009 Sep 15;122(Pt 18):3351-7.
Alexaki VI, Charalampopoulos I, Panayotopoulou M, Kampa M, Gravanis A, Castanas E. Dehydroepiandrosterone protects human keratinocytes against apoptosis through membrane binding sites. Exp Cell Res, 2009, 315(3): 2275-83
Vilar M*, Charalampopoulos I*, Kenchappa RS*, Simi A*, Karaca E, Reversi A, Choi S, Bothwell M, Mingarro I, Friedman W, Schiavo G, Bastiaens P, Verveer P, Carter BD, Ibáñez CF. Activation of the p75 neurotrophin receptor through conformational rearrangement of disulphide-linked receptor dimmers. Neuron, 2009, 62(1): 72-83 (* equal contributors)
Papadopoulou N, Charalampopoulos I, Alevizopoulos K, Gravanis A, Stournaras C. Actin reorganization through Rho/Rock/Limk2 mediates androgen membrane receptor-induced apoptosis of DU145 human prostate cancer cells. Mol Cancer, 2008, 7:88
Charalampopoulos I, Remboutsika E, Margioris AN, Gravanis A. Neurosteroids as endogenous modulators of neurogenesis and neuronal survival. Trends Endocrinol Metab. 2008, 19(8):300-7.
Charalampopoulos I, Margioris AN, Gravanis A. Dehydroepiandrosterone (DHEA) affects neuronal survival via binding to a specific membrane receptor which triggers multiple but integrated genomic and non-genomic pro-survival signaling pathways. J Neurochem. 2008, 107(5):1457-69.
Papadopoulou N, Charalampopoulos I, Alevizopoulos K, Gravanis A, Stournaras C. Actin reorganization through Rho/Rock/Limk2 mediates androgen membrane receptor-induced apoptosis of DU145 human prostate cancer cells. Exp Cell Res, 2008
Dermitzaki E, Tsatsanis C, Minas V, Chatzaki E, Charalampopoulos I, Venihaki M, Androulidaki A, Lambropoulou M, Spiess J, Michalodimitrakis E, Gravanis A, Margioris AN. Corticotropin releasing hormone (CRF) and urocortins differentially regulate catecholamine secretion in human and rat adrenals, in a CRF receptor type specific manner. Endocrinology. 2007, 148:1524-38
Charalampopoulos I, Androulidaki A, Minas V, Chatzaki E, Tsatsanis C, Notas G, Xidakis C, Kolios G, Kouroumalis E, Margioris AN, Gravanis A. Neuropeptide urocortin and its receptors are expressed in rat kupffer cells. Neuroendocrinology. 2006, 84:49-57. (Cover story of the Journal)
Alexaki VI, Dermitzaki E, Charalampopoulos I, Kampa M, Nifli AP, Gravanis A, Margioris AN, Castanas E. Neuronal differentiation of PC12 cells abolishes the expression of membrane androgen receptors. Exp Cell Res. 2006, 312:2745-56.
Kampa M, Kogia C, Theodoropoulos PA, Anezinis P, Charalampopoulos I, Papakonstanti EA, Stathopoulos EN, Hatzoglou A, Stournaras C, Gravanis A, Castanas E. Activation of membrane androgen receptors potentiates the antiproliferative effects of paclitaxel on human prostate cancer cells. Mol Cancer Ther. 2006, 5:1342-51.
Bamberger CM, Minas V, Bamberger AM, Charalampopoulos I, Fragouli Y, Schulte HM, Makrigiannakis A. Expression of urocortin in the extravillous human trophoblast at the implantation site. Placenta. 2007, 28:127-32.
Tsatsanis C, Androulidaki A, Alissafi T, Charalampopoulos I, Dermitzaki E, Roger T, Gravanis A, Margioris AN. Corticotropin-releasing factor and the urocortins induce the expression of TLR4 in macrophages via activation of the transcription factors PU.1 and AP-1. J Immunol. 2006, 176:1869-77.
Alexaki VI*, Charalampopoulos I*, Kampa M, Nifli AP, Hatzoglou A, Gravanis A, Castanas E. Activation of membrane estrogen receptors induce pro-survival kinases. J Steroid Biochem Mol Biol. 2006, 98:97-110. (* equal contributors)
Charalampopoulos I*, Alexaki VI*, Lazaridis I, Dermitzaki E, Avlonitis N, Tsatsanis C, Calogeropoulou T, Margioris AN, Castanas E, Gravanis A. G protein-associated, specific membrane binding sites mediate the neuroprotective effect of dehydroepiandrosterone. FASEB J. 2006, 20:577-9. (* equal contributors)
Bamberger AM, Minas V, Kalantaridou SN, Radde J, Sadeghian H, Loning T, Charalampopoulos I, Brummer J, Wagener C, Bamberger CM, Schulte HM, Chrousos GP, Makrigiannakis A. Corticotropin-releasing hormone modulates human trophoblast invasion through carcinoembryonic antigen-related cell adhesion molecule-1 regulation. Am J Pathol. 2006, 168:141-50.
Charalampopoulos I, Alexaki VI, Tsatsanis C, Minas V, Dermitzaki E, Lasaridis I, Vardouli L, Stournaras C, Margioris AN, Castanas E, Gravanis A. Neurosteroids as endogenous inhibitors of neuronal cell apoptosis in aging. Ann N Y Acad Sci. 2006, 1088:139-52.
Tsatsanis C, Zacharioudaki V, Androulidaki A, Dermitzaki E, Charalampopoulos I, Minas V, Gravanis A, Margioris AN. Peripheral factors in the metabolic syndrome: the pivotal role of adiponectin. Ann N Y Acad Sci. 2006, 1083:185-95.
Tsatsanis C, Zacharioudaki V, Androulidaki A, Dermitzaki E, Charalampopoulos I, Minas V, Gravanis A, Margioris AN. Adiponectin induces TNF-alpha and IL-6 in macrophages and promotes tolerance to itself and other pro-inflammatory stimuli. Biochem Biophys Res Commun. 2005, 335:1254-63.
Tsatsanis C, Androulidaki A, Dermitzaki E, Charalampopoulos I, Spiess J, Gravanis A, Margioris AN. Urocortin 1 and Urocortin 2 induce macrophage apoptosis via CRFR2. FEBS Lett. 2005, 579:4259-64.
Kampa M, Nifli AP*, Charalampopoulos I*, Alexaki VI*, Theodoropoulos PA, Stathopoulos EN, Gravanis A, Castanas E. Opposing effects of estradiol- and testosterone-membrane binding sites on T47D breast cancer cell apoptosis. Exp Cell Res. 2005, 307:41-51. (* equal contributors)
Charalampopoulos I, Dermitzaki E, Vardouli L, Tsatsanis C, Stournaras C, Margioris AN, Gravanis A. Dehydroepiandrosterone sulfate and allopregnanolone directly stimulate catecholamine production via induction of tyrosine hydroxylase and secretion by affecting actin polymerization. Endocrinology. 2005, 146:3309-18.
Dermitzaki E, Tsatsanis C, Charalampopoulos I, Androulidaki A, Alexaki VI, Castanas E, Gravanis A, Margioris AN. Corticotropin-releasing hormone activates protein kinase C in an isoenzyme-specific manner. Biochem Biophys Res Commun. 2005, 327:828-36.
Hatzoglou A*, Kampa M*, Kogia C*, Charalampopoulos I, Theodoropoulos PA, Anezinis P, Dambaki C, Papakonstanti EA, Stathopoulos EN, Stournaras C, Gravanis A, Castanas E. Membrane androgen receptor activation induces apoptotic regression of human prostate cancer cells in vitro and in vivo. J Clin Endocrinol Metab. 2005, 90:893-903. (* equal contributors)
Alexaki VI, Charalampopoulos I, Kampa M, Vassalou H, Theodoropoulos P, Stathopoulos EN, Hatzoglou A, Gravanis A, Castanas E. Estrogen exerts neuroprotective effects via membrane estrogen receptors and rapid Akt/NOS activation. FASEB J. 2004, 18:1594-6.
Charalampopoulos I, Tsatsanis C, Dermitzaki E, Alexaki VI, Castanas E, Margioris AN, Gravanis A. Dehydroepiandrosterone and allopregnanolone protect sympathoadrenal medulla cells against apoptosis via antiapoptotic Bcl-2 proteins. Proc Natl Acad Sci U S A. 2004, 101:8209-14.
Chatzaki E, Charalampopoulos I, Leontidis C, Mouzas IA, Tzardi M, Tsatsanis C, Margioris AN, Gravanis A. Urocortin in human gastric mucosa: relationship to inflammatory activity. J Clin Endocrinol Metab. 2003, 88:478-83.
Zoumakis E, Chatzaki E, Charalampopoulos I, Margioris AN, Angelakis E, Koumantakis E, Gravanis A. Cycle and age-related changes in corticotropin-releasing hormone levels in human endometrium and ovaries. Gynecol Endocrinol. 2001, 15:98-102.