{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:58:58Z","timestamp":1788454738335,"version":"build-2803163510"},"reference-count":84,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"General Secretariat for Research & Technology, program ARISTEIA I \u201cMyelin Tag\u201d Project 593"},{"name":"Hellenic Academy of Neuroimmunology"},{"name":"ERC01 National Initiative"},{"DOI":"10.13039\/501100003448","name":"General Secretariat for Research & Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003448","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>BNN27, a member of a chemical library of C17\u2010spiroepoxy derivatives of the neurosteroid DHEA, has been shown to regulate neuronal survival through its selective interaction with NGF receptors (TrkA and p75<jats:sup>NTR<\/jats:sup>), but its role on glial populations has not been studied. Here, we present evidence that BNN27 provides trophic action (rescue from apoptosis), in a TrkA\u2010dependent manner, to mature oligodendrocytes when they are challenged with the cuprizone toxin in culture. BNN27 treatment also increases oligodendrocyte maturation and diminishes microglia activation <jats:italic>in vitro<\/jats:italic>. The effect of BNN27 in the cuprizone mouse model of demyelination <jats:italic>in vivo<\/jats:italic> has also been investigated. In this model, that does not directly involve the adaptive immune system, BNN27 can protect from demyelination without affecting the remyelinating process. BNN27 preserves mature oligodendrocyte during demyelination, while reducing microgliosis and astrogliosis. Our findings suggest that BNN27 may serve as a lead molecule to develop neurotrophin\u2010like blood\u2013brain barrier (BBB)\u2010permeable protective agents of oligodendrocyte populations and myelin, with potential applications in the treatment of demyelinating disorders.<\/jats:p>","DOI":"10.1002\/glia.23170","type":"journal-article","created":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T07:34:16Z","timestamp":1496302456000},"page":"1376-1394","source":"Crossref","is-referenced-by-count":31,"title":["The novel synthetic microneurotrophin BNN27 protects mature oligodendrocytes against cuprizone\u2010induced death, through the NGF receptor TrkA"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1469-2004","authenticated-orcid":false,"given":"Giulia","family":"Bonetto","sequence":"first","affiliation":[{"name":"Department of Basic Science Faculty of Medicine, University of Crete  Crete Greece"},{"name":"Institute of Molecular Biology &amp; Biotechnology \u2010 FoRTH Heraklion Crete Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3415-7332","authenticated-orcid":false,"given":"Ioannis","family":"Charalampopoulos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine, University of Crete  Crete Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achille","family":"Gravanis","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology &amp; Biotechnology \u2010 FoRTH Heraklion Crete Greece"},{"name":"Department of Pharmacology Faculty of Medicine, University of Crete  Crete Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domna","family":"Karagogeos","sequence":"additional","affiliation":[{"name":"Department of Basic Science Faculty of Medicine, University of Crete  Crete Greece"},{"name":"Institute of Molecular Biology &amp; Biotechnology \u2010 FoRTH Heraklion Crete Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601038"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509438102"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90440-I"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn738"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-30-09824.2003"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2010.11.001"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0248-4900(91)90045-O"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.8.4089"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-013-9380-9"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.08.001"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(90)90073-V"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-1009-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm900468p"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/383716a0"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.251543398"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1078"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05732.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0306631101"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-20-06433.1996"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215549704500702"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/frne.1999.0188"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2003.11.008"},{"key":"e_1_2_7_24_1","article-title":"A personalized approach in progressive multiple sclerosis: The current status of disease modifying therapies (DMTs) and future perspectives","volume":"17","author":"D'Amico E.","year":"2016","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.12.7094"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22736"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2007.03.040"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01881.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2012.02284.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164103"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl075"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-009-0099-3"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/micr.10039"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00073"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199804)22:4<401::AID-GLIA9>3.0.CO;2-5"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.14573\/altex.2009.2.83"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161629"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00954.x"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0841-12.2012"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0591-3"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7770777"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2006.01.020"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.03.010"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906678106"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001051"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.05.001"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90286-L"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2007.00879.x"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1996.tb00854.x"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(96)00283-3"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2006.03.004"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2001.tb00385.x"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.85.3.890"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.03.005"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.11.078"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-6-58"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00214-X"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21266"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70264-9"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.75.4.1002"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2016.09.007"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1596"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00512"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.112929"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/1043-2760(94)90114-7"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.4.942-964.2004"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1994.tb00981.x"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.03.050"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802218105"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201404154"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2009.00271.x"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws262"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10154"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M910419199"},{"key":"e_1_2_7_75_1","first-page":"e3814","article-title":"Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue","author":"Tamashiro T. T.","year":"2012","journal-title":"Journal of Visualized Experiment"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.1807"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.1.91"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.10.1799"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00492"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050906"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/360753a0"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2010.01.013"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2014.06.017"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2011.04.022"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.8.6907"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.23170","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.23170","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T11:50:40Z","timestamp":1696333840000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.23170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6]]},"references-count":84,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["10.1002\/glia.23170"],"URL":"https:\/\/doi.org\/10.1002\/glia.23170","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6]]}}}