DC Field | Value | Language |
dc.contributor.author | Raasch, Katharina | |
dc.contributor.author | Malecki, Edith | |
dc.contributor.author | Siemann, Maria | |
dc.contributor.author | Martinez, Malayko M. | |
dc.contributor.author | Heinisch, Juergen J. | |
dc.contributor.author | Mueller, Janine | |
dc.contributor.author | Bakota, Lidia | |
dc.contributor.author | Kaltschmidt, Christian | |
dc.contributor.author | Kaltschmidt, Barbara | |
dc.contributor.author | Rosemeyer, Helmut | |
dc.contributor.author | Brandt, Roland | |
dc.date.accessioned | 2021-12-23T16:08:26Z | - |
dc.date.available | 2021-12-23T16:08:26Z | - |
dc.date.issued | 2015 | |
dc.identifier.issn | 17470277 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/8295 | - |
dc.description.abstract | Nucleoside analogs (NSAs) were among the first chemotherapeutic agents and could also be useful for the manipulation of cell fate. To investigate the potential of NSAs for the induction of neuronal differentiation, we developed a novel phenotypic assay based on a human neuron-committed teratocarcinoma cell line (NT2) as a model for neuronal progenitors and constructed a NT2-based reporter cell line that expressed eGFP under the control of a neuron-specific promoter. We tested 38 structurally related NSAs and determined their activity to induce neuronal differentiation by immunocytochemistry of neuronal marker proteins, live cell imaging, fluorometric detection and immunoblot analysis. We identified twelve NSAs, which induced neuronal differentiation to different extents. NSAs with highest activity carried a halogen substituent at their pyrimidine nucleobase and an unmodified or 2'-O-methyl substituted 2-deoxy-beta-D-ribofuranosyl residue as glyconic moiety. Cladribine, a purine nucleoside with similar structural features and in use to treat leukemia and multiple sclerosis, induced also differentiation of adult human neural crest-derived stem cells. Our results suggest that NSAs could be useful for the manipulation of neuronal cell fate in cell replacement therapy or treatment of neuro-degenerative disorders. The data on the structure and function relationship will help to design compounds with increased activity and low toxicity. | |
dc.description.sponsorship | Interdisciplinary Graduate College ``Cell and Tissue Differentiation from an Integrative Perspective'' at the University of Osnabruck; B. Braun AG (Melsungen, Germany); We thank Xu Xu for help with developing the fluorometric analysis, Frederik Sundermann, Giray Korkmaz and Marta Swierczek for initial experiments on the effect of synthetic nucleoside analogs, Angelika Hilderink and Vanessa Herkenhoff for technical assistance. The work was supported by the Interdisciplinary Graduate College ``Cell and Tissue Differentiation from an Integrative Perspective'' at the University of Osnabruck. E.M. and H.R. gratefully acknowledge financial support by the B. Braun AG (Melsungen, Germany). | |
dc.language.iso | en | |
dc.publisher | WILEY | |
dc.relation.ispartof | CHEMICAL BIOLOGY & DRUG DESIGN | |
dc.subject | adult human stem cell | |
dc.subject | ANTIVIRAL COMPOUNDS | |
dc.subject | Biochemistry & Molecular Biology | |
dc.subject | CHEMICAL APPROACH | |
dc.subject | Chemistry, Medicinal | |
dc.subject | cladribine | |
dc.subject | CNS MODEL NEURONS | |
dc.subject | CORTICAL-NEURONS | |
dc.subject | CYTOSTATIC 5-FLUOROURIDINE | |
dc.subject | HERPES-SIMPLEX VIRUS | |
dc.subject | human model neuron | |
dc.subject | INTERFERON-ALPHA | |
dc.subject | neuronal differentiation | |
dc.subject | NTERA-2 CELLS | |
dc.subject | nucleoside analog | |
dc.subject | Pharmacology & Pharmacy | |
dc.subject | RETINOIC ACID | |
dc.subject | SMALL MOLECULES | |
dc.title | Identification of Nucleoside Analogs as Inducers of Neuronal Differentiation in a Human Reporter Cell Line and Adult Stem Cells | |
dc.type | journal article | |
dc.identifier.doi | 10.1111/cbdd.12488 | |
dc.identifier.isi | ISI:000359215900001 | |
dc.description.volume | 86 | |
dc.description.issue | 2 | |
dc.description.startpage | 129 | |
dc.description.endpage | 143 | |
dc.contributor.orcid | 0000-0003-0101-1257 | |
dc.contributor.orcid | 0000-0002-8777-5006 | |
dc.contributor.orcid | 0000-0003-3773-4625 | |
dc.contributor.researcherid | G-3801-2017 | |
dc.identifier.eissn | 17470285 | |
dc.publisher.place | 111 RIVER ST, HOBOKEN 07030-5774, NJ USA | |
dcterms.isPartOf.abbreviation | Chem. Biol. Drug Des. | |
crisitem.author.dept | Institut für Chemie neuer Materialien | - |
crisitem.author.deptid | institute11 | - |
crisitem.author.orcid | 0000-0003-0101-1257 | - |
crisitem.author.parentorg | FB 05 - Biologie/Chemie | - |
crisitem.author.grandparentorg | Universität Osnabrück | - |
crisitem.author.netid | RoHe783 | - |
crisitem.author.netid | BrRo587 | - |