Kügler, Sebastian

[["dc.bibliographiccitation.firstpage","247"],["dc.bibliographiccitation.issue","3-4"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","264"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Psol, Maryna"],["dc.contributor.author","Darvas, Sofia Guerin"],["dc.contributor.author","Leite, Kristian"],["dc.contributor.author","Mahajani, Sameehan U"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Kügler, Sebastian"],["dc.date.accessioned","2021-07-05T14:57:32Z"],["dc.date.available","2021-07-05T14:57:32Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Beta (ß)-synuclein (ß-Syn) has long been considered to be an attenuator for the neuropathological effects caused by the Parkinson’s disease-related alpha (α)-synuclein (α-Syn) protein. However, recent studies demonstrated that overabundant ß-Syn can form aggregates and induce neurodegeneration in central nervous system (CNS) neurons in vitro and in vivo, albeit at a slower pace as compared with α-Syn. Here, we demonstrate that ß-Syn mutants V70M, detected in a sporadic case of dementia with Lewy bodies (DLB), and P123H, detected in a familial case of DLB, robustly aggravate the neurotoxic potential of ß-Syn. Intriguingly, the two mutations trigger mutually exclusive pathways. ß-Syn V70M enhances morphological mitochondrial deterioration and degeneration of dopaminergic and non-dopaminergic neurons, but it has no influence on neuronal network activity. Conversely, ß-Syn P123H silences neuronal network activity, but it does not aggravate neurodegeneration. ß-Syn wild type (WT), V70M and P123H formed proteinase K-resistant intracellular fibrils within neurons, albeit with less stable C-termini as compared with α-Syn. Under cell-free conditions, ß-Syn V70M demonstrated a much slower pace of fibril formation as compared with WT ß-Syn, and P123H fibrils present with a unique phenotype characterized by large numbers of short, truncated fibrils. Thus, it is possible that V70M and P123H cause structural alterations in ß-Syn, which are linked to their distinct neuropathological profiles. The extent of the lesions caused by these neuropathological profiles is almost identical to that of overabundant α-Syn and is thus likely to be directly involved into the etiology of DLB. Overall, this study provides insights into distinct disease mechanisms caused by mutations of ß-Syn."],["dc.description.abstract","Abstract Beta (ß)-synuclein (ß-Syn) has long been considered to be an attenuator for the neuropathological effects caused by the Parkinson’s disease-related alpha (α)-synuclein (α-Syn) protein. However, recent studies demonstrated that overabundant ß-Syn can form aggregates and induce neurodegeneration in central nervous system (CNS) neurons in vitro and in vivo, albeit at a slower pace as compared with α-Syn. Here, we demonstrate that ß-Syn mutants V70M, detected in a sporadic case of dementia with Lewy bodies (DLB), and P123H, detected in a familial case of DLB, robustly aggravate the neurotoxic potential of ß-Syn. Intriguingly, the two mutations trigger mutually exclusive pathways. ß-Syn V70M enhances morphological mitochondrial deterioration and degeneration of dopaminergic and non-dopaminergic neurons, but it has no influence on neuronal network activity. Conversely, ß-Syn P123H silences neuronal network activity, but it does not aggravate neurodegeneration. ß-Syn wild type (WT), V70M and P123H formed proteinase K-resistant intracellular fibrils within neurons, albeit with less stable C-termini as compared with α-Syn. Under cell-free conditions, ß-Syn V70M demonstrated a much slower pace of fibril formation as compared with WT ß-Syn, and P123H fibrils present with a unique phenotype characterized by large numbers of short, truncated fibrils. Thus, it is possible that V70M and P123H cause structural alterations in ß-Syn, which are linked to their distinct neuropathological profiles. The extent of the lesions caused by these neuropathological profiles is almost identical to that of overabundant α-Syn and is thus likely to be directly involved into the etiology of DLB. Overall, this study provides insights into distinct disease mechanisms caused by mutations of ß-Syn."],["dc.identifier.doi","10.1093/hmg/ddab036"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87669"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-441"],["dc.relation.eissn","1460-2083"],["dc.relation.issn","0964-6906"],["dc.title","Dementia with Lewy bodies—associated ß-synuclein mutations V70M and P123H cause mutation-specific neuropathological lesions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","89"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Virology"],["dc.bibliographiccitation.lastpage","95"],["dc.bibliographiccitation.volume","311"],["dc.contributor.author","Kügler, S"],["dc.contributor.author","Schöll, U"],["dc.contributor.author","Zolotukhin, S"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Bähr, Mathias"],["dc.date.accessioned","2021-06-01T10:50:07Z"],["dc.date.available","2021-06-01T10:50:07Z"],["dc.date.issued","2003"],["dc.description.abstract","Adeno-associated- (AAV) based vectors are promising tools for gene therapy applications in several organs, including the brain, but are limited by their small genome size. Two short promoters, the human synapsin 1 gene promoter (hSYN) and the murine cytomegalovirus immediate early promoter (mCMV), were evaluated in bicistronic AAV-2 vectors for their expression profiles in cultured primary brain cells and in the rat brain. Whereas transgene expression from the hSYN promoter was exclusively neuronal, the murine CMV promoter targeted expression mainly to astrocytes in vitro and showed weak transgene expression in vivo in retinal and cortical neurons, but strong expression in thalamic neurons. We propose that neuron specific transgene expression in combination with enhanced transgene capacity will further substantially improve AAV based vector technology. (C) 2003 Elsevier Science (USA). All rights reserved."],["dc.identifier.doi","10.1016/S0042-6822(03)00162-4"],["dc.identifier.gro","3144097"],["dc.identifier.isi","000184042900010"],["dc.identifier.pmid","12832206"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86537"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0042-6822"],["dc.title","Differential transgene expression in brain cells in vivo and in vitro from AAV-2 vectors with small transcriptional control units"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","479"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biochemical and Biophysical Research Communications"],["dc.bibliographiccitation.lastpage","483"],["dc.bibliographiccitation.volume","265"],["dc.contributor.author","Roth, W"],["dc.contributor.author","Isenmann, Stefan"],["dc.contributor.author","Naumann, U."],["dc.contributor.author","Kugler, S."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Dichgans, J."],["dc.contributor.author","Ashkenazi, A."],["dc.contributor.author","Weller, M"],["dc.date.accessioned","2017-09-07T11:47:27Z"],["dc.date.available","2017-09-07T11:47:27Z"],["dc.date.issued","1999"],["dc.description.abstract","Glioblastoma multiforme is a lethal neoplasm refractory to radiochemotherapy, Although glioma cells undergo apoptosis when exposed to the death ligand, CD95 (Fas/APO-1) ligand, the therapeutic use of CD95L is considered impossible because of lethal side effects. Here, we report that the locoregional application of Apoa ligand (Apo2L) exerts strong antitumor activity on preestablished intracranially growing human U87MG glioma xenografts in athymic mice. Two repetitive intratumoral injections of 2 mu g Apo2L resulted in long-term survival of mice (>100 days), whereas the median survival of mock-treated mice was 36 days. The assessment of tumor volumes at 21 and 35 days after inoculation showed complete eradication of glioma xenografts in Apo2L-treated mice. Histology and TUNEL assay confirmed the induction of apoptosis by Apo2L in glioma cells in vivo. Importantly, the intracerebral injection of Apo2L does not result in acute or delayed neurotoxicity. We propose that a phase 1 trial of intralesional Apo2L therapy for human glioblastoma multiforme is warranted. (C) 1999 Academic Press."],["dc.identifier.doi","10.1006/bbrc.1999.1693"],["dc.identifier.gro","3144435"],["dc.identifier.isi","000083899100038"],["dc.identifier.pmid","10558893"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2059"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Inc"],["dc.relation.issn","0006-291X"],["dc.title","Locoregional Apo2L/TRAIL eradicates intracranial human malignant glioma xenografts in athymic mice in the absence of neurotoxicity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","123"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","133"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Straten, G"],["dc.contributor.author","Schmeer, C."],["dc.contributor.author","Kretz, A."],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Kugler, S."],["dc.contributor.author","Schulz, Joerg B."],["dc.contributor.author","Gravel, C."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Isenmann, Stefan"],["dc.date.accessioned","2017-09-07T11:45:15Z"],["dc.date.available","2017-09-07T11:45:15Z"],["dc.date.issued","2002"],["dc.description.abstract","Following transection of the optic nerve (ON) in the adult rat, retinal ganglion cells (RGCs) undergo degeneration, and within 14 days 85% of axotomized RGCs die by apoptosis. Adenoviral delivery of the mammalian caspase inhibitor X-chromosome-linked inhibitor of apoptosis (Ad.XIAP) to the ON stump leads to expression exclusively in RGCs and rescues 18.9% of the RGCs that would degenerate without treatment. Following adenoviral vector injection into the vitreous body, bioactive glial cell line-derived neurotrophic factor (Ad.GDNF) is expressed in the retina and secreted to rescue 22.8% of lesioned RGCs. Here we report that coadministration of Ad.XIAP retrogradely directed to RGCs and intravitreal Ad.GDNF acts synergistically to protect axotomized RGCs. Combination treatment rescued 47.3% of RGCs that would undergo apoptosis without any treatment as opposed to 37.4% that would be expected if the two treatments acted independently. While without treatment only 15% of axotomized RGCs would survive, combination treatment resulted in survival of 55.4% of the total RGC population. These findings underline the neuroprotective potential of synergistic effects of a combination of different treatment strategies. (C) 2002 Elsevier Science (USA)."],["dc.identifier.doi","10.1006/nbdi.2002.0543"],["dc.identifier.gro","3144173"],["dc.identifier.isi","000179314100011"],["dc.identifier.pmid","12460552"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1768"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0969-9961"],["dc.title","Potential synergistic protection of retinal ganglion cells from axotomy-induced apoptosis by adenoviral administration of glial cell line-derived neurotrophic factor and X-chromosome-linked inhibitor of apoptosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","109"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","118"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Taschenberger, G."],["dc.contributor.author","Toloe, J."],["dc.contributor.author","Tereshchenko, J."],["dc.contributor.author","Akerboom, J."],["dc.contributor.author","Wales, P."],["dc.contributor.author","Benz, R."],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Outeiro, T. F."],["dc.contributor.author","Looger, L. L."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Zweckstetter, M."],["dc.contributor.author","Kügler, Sebastian"],["dc.date.accessioned","2017-09-07T11:47:39Z"],["dc.date.available","2017-09-07T11:47:39Z"],["dc.date.issued","2013"],["dc.description.abstract","ObjectiveWhereas the contribution of -synuclein to neurodegeneration in Parkinson disease is well accepted, the putative impact of its close homologue, -synuclein, is enigmatic. -Synuclein is widely expressed throughout the central nervous system, as is -synuclein, but the physiological functions of both proteins remain unknown. Recent findings have supported the view that -synuclein can act as an ameliorating regulator of -synuclein-induced neurotoxicity, having neuroprotective rather than neurodegenerative capabilities, and being nonaggregating due to the absence of most of the aggregation-promoting NAC domain. However, a mutation of -synuclein linked to dementia with Lewy bodies rendered the protein neurotoxic in transgenic mice, and fibrillation of -synuclein has been demonstrated in vitro. MethodsNeurotoxicity and aggregation properties of -, -, and -synuclein were comparatively elucidated in the rat nigro-striatal projection and in cultured neurons. ResultsSupporting the hypothesis that -synuclein can act as a neurodegeneration-inducing factor, we demonstrated that wild-type -synuclein is neurotoxic for cultured primary neurons. Furthermore, -synuclein formed proteinase K-resistant aggregates in dopaminergic neurons in vivo, leading to pronounced and progressive neurodegeneration in rats. Expression of -synuclein caused mitochondrial fragmentation, but this fragmentation did not render mitochondria nonfunctional in terms of ion handling and respiration even at late stages of neurodegeneration. A comparison of the neurodegenerative effects induced by -, -, and -synuclein revealed that -synuclein was eventually as neurotoxic as -synuclein for nigral dopaminergic neurons, whereas -synuclein proved to be nontoxic and had very low aggregation propensity. InterpretationOur results suggest that the role of -synuclein as a putative modulator of neuropathology in aggregopathies like Parkinson disease and dementia with Lewy bodies needs to be revisited. Ann Neurol 2013;74:109-118"],["dc.identifier.doi","10.1002/ana.23905"],["dc.identifier.gro","3142329"],["dc.identifier.isi","000329198600014"],["dc.identifier.pmid","23536356"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7075"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1531-8249"],["dc.relation.issn","0364-5134"],["dc.title","β-Synuclein Aggregates and Induces Neurodegeneration in Dopaminergic Neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","335"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Experimental Brain Research"],["dc.bibliographiccitation.lastpage","342"],["dc.bibliographiccitation.volume","161"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Scholl, U."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Kugler, S."],["dc.date.accessioned","2017-09-07T11:54:31Z"],["dc.date.available","2017-09-07T11:54:31Z"],["dc.date.issued","2005"],["dc.description.abstract","The Semliki Forest virus (SFV) system has been shown to be highly efficient in transduction of cell lines and primary cells. We employed a novel \"noncytotoxic\" SFV(PD) vector for transduction of primary ventral midbrain floor cultures in vitro and rat substantia nigra in vivo. Rapid protein expression was noted with preferential transduction of neuronal cells including the dopaminergic subpopulation. To examine the suitability of the SFV vector system for functional gene expression, SFV(PD) vectors encoding for antiapoptotic proteins Bcl-X-L and XIAP were designed. Despite effective transgene expression, SFV(PD) vectors were unable to rescue dopaminergic neurons from MPP+-induced apoptosis. In vivo, virus injection into substantia nigra resulted in fast onset of transgene expression, but elicited an activation of microglia and an inflammation response. We conclude that the use of novel SFV(PD) vectors is currently limited by persistent neurotoxicity of the vector system. Although SFV(PD) vectors may be useful for protein localization studies in dopaminergic neurons, functional applications will require the development of even less cytopathic vector systems."],["dc.identifier.doi","10.1007/s00221-004-2077-9"],["dc.identifier.gro","3143883"],["dc.identifier.isi","000227236900009"],["dc.identifier.pmid","15502982"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1446"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0014-4819"],["dc.title","Functional applications of novel Semliki Forest virus vectors are limited by vector toxicity in cultures of primary neurons in vitro and in the substantia nigra in vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1569"],["dc.bibliographiccitation.issue","22"],["dc.bibliographiccitation.journal","Gene Therapy"],["dc.bibliographiccitation.lastpage","1578"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Shevtsova, Z."],["dc.contributor.author","Malik, I."],["dc.contributor.author","Garrido, M."],["dc.contributor.author","Schoell, U."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Kügler, S"],["dc.date.accessioned","2017-09-07T11:52:27Z"],["dc.date.available","2017-09-07T11:52:27Z"],["dc.date.issued","2006"],["dc.description.abstract","To elucidate effective and long-lasting neuroprotective strategies, we analysed a combination of mitochondrial protection and neurotrophic support in two well-defined animal models of neurodegeneration, traumatic lesion of optic nerve and complete 6-hydroxydopamine (6-OHDA) lesion of nigrostriatal pathway. Neuroprotection by BclX(L), Glial cell line-derived neurotrophic factor (GDNF) or BclX(L) plus GDNF co-expression were studied at 2 weeks and at 6-8 weeks after lesions. In both lesion paradigms, the efficacy of this combination approach significantly differed depending on post-lesion time. We show that BclX(L) expression is more important for neuronal survival in the early phase after lesions, whereas GDNF-mediated neuroprotection becomes more prominent in the advanced state of neurodegeneration. BclX(L) expression was not sufficient to finally inhibit degeneration of deafferentiated central nervous system neurons. Long-lasting GDNF-mediated neuroprotection depended on BclX(L) co-expression in the traumatic lesion paradigm, but was independent of BclX(L) in the 6-OHDA lesion model. The results demonstrate that neuroprotection studies in animal models of neurodegenerative diseases should generally be performed over extended periods of time in order to reveal the actual potency of a therapeutic approach."],["dc.identifier.doi","10.1038/sj.gt.3302822"],["dc.identifier.gro","3143599"],["dc.identifier.isi","000241818000003"],["dc.identifier.pmid","16838029"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1131"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0969-7128"],["dc.title","Potentiation of in vivo neuroprotection by BclX(L) and GDNF co-expression depends on post-lesion time in deafferentiated CNS neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","534"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Molecular Therapy"],["dc.bibliographiccitation.lastpage","543"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Drinkut, A."],["dc.contributor.author","Tereshchenko, Y."],["dc.contributor.author","Schulz, J. B."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Kügler, Sebastian"],["dc.date.accessioned","2017-09-07T11:48:58Z"],["dc.date.available","2017-09-07T11:48:58Z"],["dc.date.issued","2012"],["dc.description.abstract","Current gene therapy approaches for Parkinson's -disease (PD) deliver neurotrophic factors like glial cell line-derived neurotrophic factor (GDNF) or neurturin via neuronal transgene expression. Since these potent signaling-inducing neurotrophic factors can be distributed through long-distance neuronal projections to unaffected brain sites, this mode of delivery may eventually cause side effects. To explore a localized and thus potentially safer alternative for gene therapy of PD, we expressed GDNF exclusively in astrocytes and evaluated the efficacy of this approach in the mouse 1-methyl-4-phenyl-1,2,3, -6-tetrahydropyridine (MPTP) and rat -6-hydroxy-dopamine (6-OHDA) models of PD. In terms of protection of dopaminergic cell bodies and projections, dopamine (DA) synthesis and behaviour, -astrocyte-derived GDNF demonstrated the same efficacy as neuron-derived GDNF. In terms of safety, unilateral striatal GDNF expression in astrocytes did not result in delivery of bio-active GDNF to the contralateral hemispheres (potential off-target sites) as happened when GDNF was expressed in neurons. Thus, astrocytic GDNF expression represents a localized but efficient alternative to current gene therapeutic strategies for the treatment of PD, especially if viral vectors with enhanced tissue -penetration are considered. Astrocytic neurotrophic -factor expression may open new venues for neurotrophic factor-based gene therapy targeting severe diseases of the brain. Received 19 May 2011; accepted 18 October 2011; published online 15 November 2011. doi:10.1038/mt.2011.249"],["dc.identifier.doi","10.1038/mt.2011.249"],["dc.identifier.gro","3142573"],["dc.identifier.isi","000300943700007"],["dc.identifier.pmid","22086235"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8589"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8939"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1525-0016"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Efficient Gene Therapy for Parkinson's Disease Using Astrocytes as Hosts for Localized Neurotrophic Factor Delivery"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","245"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Biochemical and Biophysical Research Communications"],["dc.bibliographiccitation.lastpage","253"],["dc.bibliographiccitation.volume","341"],["dc.contributor.author","Malik, I."],["dc.contributor.author","Garrido, M."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Kügler, S."],["dc.contributor.author","Michel, U."],["dc.date.accessioned","2017-09-07T11:53:12Z"],["dc.date.available","2017-09-07T11:53:12Z"],["dc.date.issued","2006"],["dc.description.abstract","RNAinterference (RNAi) has developed within a short time from an area of basic research occupied by a few experts to a widely used technical tool for reverse genetics, which is expected to have a broad utility not only in research, but also in medical and diagnostic applications. Despite its widespread use, the application of RNAi is often hampered because it difference of only a few nuclectides in the sequence of the target RNA can change the efficiency of a small interfering RNA (siRNA) from high to zero, and publicly available design tools for siRNAs are not yet perfect. We therefore developed and compared RNAi test systems based oil different promoters, reporters, and target sequences. Here, we show that fluorescence-based test systems have obvious disadvantages compared to luciferase-based test systems and that some combinations of promoter, reporter, and target sequences, although Currently in use, are not well suited for testing RNAi effects. (c) 2005 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.bbrc.2005.12.173"],["dc.identifier.gro","3143725"],["dc.identifier.isi","000235313400036"],["dc.identifier.pmid","16423323"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1271"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0006-291X"],["dc.title","Comparison of test systems for RNAinterference"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","249"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","260"],["dc.bibliographiccitation.volume","57"],["dc.contributor.author","Raina, Anupam"],["dc.contributor.author","Mahajani, Sameehan"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Kügler, Sebastian"],["dc.date.accessioned","2020-12-10T14:14:28Z"],["dc.date.available","2020-12-10T14:14:28Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s12035-019-01701-x"],["dc.identifier.eissn","1559-1182"],["dc.identifier.issn","0893-7648"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71352"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Neuronal Trans-differentiation by Transcription Factors Ascl1 and Nurr1: Induction of a Dopaminergic Neurotransmitter Phenotype in Cortical GABAergic Neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]