Tideglusib Rescues Neurite Pathology of SPG11 iPSC Derived Cortical Neurons

dc.contributor.authorPozner, Tatyana
dc.contributor.authorSchray, Annika
dc.contributor.authorRegensburger, Martin
dc.contributor.authorLie, Dieter Chichung
dc.contributor.authorSchlötzer-Schrehardt, Ursula
dc.contributor.authorWinkler, Jürgen
dc.contributor.authorTuran, Soeren
dc.contributor.authorWinner, Beate
dc.date.accessioned2020-01-15
dc.date.available2023-10-09T14:37:53Z
dc.date.created2018
dc.date.issued2020-01-15
dc.description.abstractMutations in SPG11 cause a complicated autosomal recessive form of hereditary spastic paraplegia (HSP). Mechanistically, there are indications for the dysregulation of the GSK3β/βCat signaling pathway in SPG11. In this study, we tested the therapeutic potential of the GSK3β inhibitor, tideglusib, to rescue neurodegeneration associated characteristics in an induced pluripotent stem cells (iPSCs) derived neuronal model from SPG11 patients and matched healthy controls as well as a CRISPR-Cas9 mediated SPG11 knock-out line and respective control. SPG11-iPSC derived cortical neurons, as well as the genome edited neurons exhibited shorter and less complex neurites than controls. Administration of tideglusib to these lines led to the rescue of neuritic impairments. Moreover, the treatment restored increased cell death and ameliorated the membranous inclusions in iPSC derived SPG11 neurons. Our results provide a first evidence for the rescue of neurite pathology in SPG11-HSP by tideglusib. The current lack of disease-modifying treatments for SPG11 and related types of complicated HSP renders tideglusib a candidate compound for future clinical application.en
dc.identifier.citationFrontiers in Neuroscience 12 (2018). <https://www.frontiersin.org/articles/10.3389/fnins.2018.00914/full>
dc.identifier.doihttps://doi.org/10.3389/fnins.2018.00914
dc.identifier.issn1662-453X
dc.identifier.opus-id12894
dc.identifier.urihttps://open.fau.de/handle/openfau/12894
dc.identifier.urnurn:nbn:de:bvb:29-opus4-128949
dc.language.isoen
dc.publisherFrontiers Media S.A.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.de
dc.subjectinduced pluripotent stem cell
dc.subjectneuronal culture
dc.subjectSPG11
dc.subjecttideglusib
dc.subjectGSK3β inhibitor
dc.subjecthereditary spastic paraplegia
dc.subjectCRISPR knock-out
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleTideglusib Rescues Neurite Pathology of SPG11 iPSC Derived Cortical Neuronsen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.date.prevpublished2018-12-06
local.journal.titleFrontiers in Neuroscience
local.journal.volume12
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.importimport
local.subject.sammlungUniversität Erlangen-Nürnberg / Eingespielte Open Access Artikel / Eingespielte Open Access Artikel 2020
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