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Authordc.contributor.authorArgüello, Graciela
Authordc.contributor.authorBalboa, Elisa
Authordc.contributor.authorTapia, Pablo J.
Authordc.contributor.authorCastro, Juan
Authordc.contributor.authorYáñez, María José
Authordc.contributor.authorMattar, Pamela
Authordc.contributor.authorPulgar Tejo, Rodrigo Enrique
Authordc.contributor.authorZanlungo, Silvana
Cita de ítemdc.identifier.citationInt. J. Mol. Sci. 2021, 22, 4220es_ES
Abstractdc.description.abstractNiemann-Pick type C disease (NPCD) is a lysosomal storage disease (LSD) characterized by abnormal cholesterol accumulation in lysosomes, impaired autophagy flux, and lysosomal dysfunction. The activation of transcription factor EB (TFEB), a master lysosomal function regulator, reduces the accumulation of lysosomal substrates in LSDs where the degradative capacity of the cells is compromised. Genistein can pass the blood-brain barrier and activate TFEB. Hence, we investigated the effect of TFEB activation by genistein toward correcting the NPC phenotype. We show that genistein promotes TFEB translocation to the nucleus in HeLa TFEB-GFP, Huh7, and SHSY-5Y cells treated with U18666A and NPC1 patient fibroblasts. Genistein treatment improved lysosomal protein expression and autophagic flux, decreasing p62 levels and increasing those of the LC3-II in NPC1 patient fibroblasts. Genistein induced an increase in beta-hexosaminidase activity in the culture media of NPC1 patient fibroblasts, suggesting an increase in lysosomal exocytosis, which correlated with a decrease in cholesterol accumulation after filipin staining, including cells treated with U18666A and NPC1 patient fibroblasts. These results support that genistein-mediated TFEB activation corrects pathological phenotypes in NPC models and substantiates the need for further studies on this isoflavonoid as a potential therapeutic agent to treat NPCD and other LSDs with neurological compromise.es_ES
Patrocinadordc.description.sponsorshipCONICYT/ANID-Chile 3160635 3190416 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1190334 11161083 MSCA-RISE-2016-Lysomod-734825es_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
Link to Licensedc.rights.uri*
Sourcedc.sourceInternational Journal of Molecular Scienceses_ES
Keywordsdc.subjectNiemann–Pick Ces_ES
Keywordsdc.subjectLysosomal storage diseaseses_ES
Keywordsdc.subjectLysosome clearancees_ES
Títulodc.titleGenistein activates transcription factor EB and corrects Niemann–Pick C phenotypees_ES
Document typedc.typeArtículo de revistaes_ES
dc.description.versiondc.description.versionVersión publicada - versión final del editores_ES
dcterms.accessRightsdcterms.accessRightsAcceso abiertoes_ES
Indexationuchile.indexArtículo de publícación WoSes_ES

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Attribution-NonCommercial-NoDerivs 3.0 United States
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 United States