dc.contributor.author
Hossini, Amir M.
dc.contributor.author
Megges, Matthias
dc.contributor.author
Prigione, Alessandro
dc.contributor.author
Lichtner, Bjoern
dc.contributor.author
Toliat, Mohammad R.
dc.contributor.author
Wruck, Wasco
dc.contributor.author
Schröter, Friederike
dc.contributor.author
Nuernberg, Peter
dc.contributor.author
Kroll, Hartmut
dc.contributor.author
Makrantonaki, Eugenia
dc.contributor.author
Zoubouliss, Christos C.
dc.contributor.author
Adjaye, James
dc.date.accessioned
2018-06-08T02:58:15Z
dc.date.available
2015-03-26T11:51:40.168Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/14229
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-18425
dc.description.abstract
Background Alzheimer’s disease (AD) is a complex, irreversible
neurodegenerative disorder. At present there are neither reliable markers to
diagnose AD at an early stage nor therapy. To investigate underlying disease
mechanisms, induced pluripotent stem cells (iPSCs) allow the generation of
patient-derived neuronal cells in a dish. Results In this study, employing iPS
technology, we derived and characterized iPSCs from dermal fibroblasts of an
82-year-old female patient affected by sporadic AD. The AD-iPSCs were
differentiated into neuronal cells, in order to generate disease-specific
protein association networks modeling the molecular pathology on the
transcriptome level of AD, to analyse the reflection of the disease phenotype
in gene expression in AD-iPS neuronal cells, in particular in the ubiquitin-
proteasome system (UPS), and to address expression of typical AD proteins. We
detected the expression of p-tau and GSK3B, a physiological kinase of tau, in
neuronal cells derived from AD-iPSCs. Treatment of neuronal cells
differentiated from AD-iPSCs with an inhibitor of γ-secretase resulted in the
down-regulation of p-tau. Transcriptome analysis of AD-iPS derived neuronal
cells revealed significant changes in the expression of genes associated with
AD and with the constitutive as well as the inducible subunits of the
proteasome complex. The neuronal cells expressed numerous genes associated
with sub-regions within the brain thus suggesting the usefulness of our in-
vitro model. Moreover, an AD-related protein interaction network composed of
APP and GSK3B among others could be generated using neuronal cells
differentiated from two AD-iPS cell lines. Conclusions Our study demonstrates
how an iPSC-based model system could represent (i) a tool to study the
underlying molecular basis of sporadic AD, (ii) a platform for drug screening
and toxicology studies which might unveil novel therapeutic avenues for this
debilitating neuronal disorder.
de
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten
dc.title
Induced pluripotent stem cell-derived neuronal cells from a sporadic
Alzheimer’s disease donor as a model for investigating AD-associated gene
regulatory networks
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
BMC Genomics. - 16 (2015), Artikel Nr. 84
dcterms.bibliographicCitation.doi
10.1186/s12864-015-1262-5
dcterms.bibliographicCitation.url
http://www.biomedcentral.com/1471-2164/16/84
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000022105
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000004710
dcterms.accessRights.openaire
open access