Michel, Uwe

[["dc.bibliographiccitation.firstpage","72"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","86"],["dc.bibliographiccitation.volume","54"],["dc.contributor.author","Ribas, Vinicius Toledo"],["dc.contributor.author","Koch, Jan C."],["dc.contributor.author","Michel, Uwe"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Lingor, Paul"],["dc.date.accessioned","2018-01-09T11:14:21Z"],["dc.date.available","2018-01-09T11:14:21Z"],["dc.date.issued","2017"],["dc.description.abstract","Axonal degeneration is one of the initial steps in many traumatic and neurodegenerative central nervous system (CNS) disorders and thus a promising therapeutic target. A focal axonal lesion is followed by acute axonal degeneration (AAD) of both adjacent axon parts, before proximal and distal parts follow different degenerative fates at later time points. Blocking calcium influx by calcium channel inhibitors was previously shown to attenuate AAD after optic nerve crush (ONC). However, it remains unclear whether the attenuation of AAD also promotes consecutive axonal regeneration. Here, we used a rat ONC model to study the effects of calcium channel inhibitors on axonal degeneration, retinal ganglion cell (RGC) survival, and axonal regeneration, as well as the molecular mechanisms involved. Application of calcium channel inhibitors attenuated AAD after ONC and preserved axonal integrity as visualized by live imaging of optic nerve axons. Consecutively, this resulted in improved survival of RGCs and improved axonal regeneration at 28 days after ONC. We show further that calcium channel inhibition attenuated lesion-induced calpain activation in the proximity of the crush and inhibited the activation of the c-Jun N-terminal kinase pathway. Pro-survival signaling via Akt in the retina was also increased. Our data thus show that attenuation of AAD improves consecutive neuronal survival and axonal regeneration and that calcium channel inhibitors could be valuable tools for therapeutic interventions in traumatic and degenerative CNS disorders."],["dc.identifier.doi","10.1007/s12035-015-9676-2"],["dc.identifier.pmid","26732591"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11580"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1559-1182"],["dc.title","Attenuation of Axonal Degeneration by Calcium Channel Inhibitors Improves Retinal Ganglion Cell Survival and Regeneration After Optic Nerve Crush"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1811"],["dc.bibliographiccitation.journal","Cell Death and Disease"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Bitow, F."],["dc.contributor.author","Haack, J."],["dc.contributor.author","D'Hedouville, Z."],["dc.contributor.author","Zhang, J-N"],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Michel, U."],["dc.contributor.author","Oliveira, L. M. A."],["dc.contributor.author","Jovin, T. M."],["dc.contributor.author","Liman, Jan"],["dc.contributor.author","Tatenhorst, L."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:43:42Z"],["dc.date.available","2017-09-07T11:43:42Z"],["dc.date.issued","2015"],["dc.description.abstract","Many neuropathological and experimental studies suggest that the degeneration of dopaminergic terminals and axons precedes the demise of dopaminergic neurons in the substantia nigra, which finally results in the clinical symptoms of Parkinson disease (PD). The mechanisms underlying this early axonal degeneration are, however, still poorly understood. Here, we examined the effects of overexpression of human wildtype alpha-synuclein (alpha Syn-WT), a protein associated with PD, and its mutant variants alpha Syn-A30P and -A53T on neurite morphology and functional parameters in rat primary midbrain neurons (PMN). Moreover, axonal degeneration after overexpression of alpha Syn-WT and -A30P was analyzed by live imaging in the rat optic nerve in vivo. We found that overexpression of alpha Syn-WT and of its mutants A30P and A53T impaired neurite outgrowth of PMN and affected neurite branching assessed by Sholl analysis in a variant-dependent manner. Surprisingly, the number of primary neurites per neuron was increased in neurons transfected with alpha Syn. Axonal vesicle transport was examined by live imaging of PMN co-transfected with EGFP-labeled synaptophysin. Overexpression of all alpha Syn variants significantly decreased the number of motile vesicles and decelerated vesicle transport compared with control. Macroautophagic flux in PMN was enhanced by alpha Syn-WT and -A53T but not by alpha Syn-A30P. Correspondingly, colocalization of alpha Syn and the autophagy marker LC3 was reduced for alpha Syn-A30P compared with the other alpha Syn variants. The number of mitochondria colocalizing with LC3 as a marker for mitophagy did not differ among the groups. In the rat optic nerve, both alpha Syn-WT and -A30P accelerated kinetics of acute axonal degeneration following crush lesion as analyzed by in vivo live imaging. We conclude that alpha Syn overexpression impairs neurite outgrowth and augments axonal degeneration, whereas axonal vesicle transport and autophagy are severely altered."],["dc.description.sponsorship","Open-Access Publikationsfonds 2015"],["dc.identifier.doi","10.1038/cddis.2015.169"],["dc.identifier.gro","3141868"],["dc.identifier.isi","000358788800011"],["dc.identifier.pmid","26158517"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12015"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1967"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","2041-4889"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Central nervous system; Molecular neuroscience; Parkinson's disease"],["dc.title","Alpha-Synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons"],["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","3472"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","FEBS Journal"],["dc.bibliographiccitation.lastpage","3483"],["dc.bibliographiccitation.volume","278"],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Barski, E."],["dc.contributor.author","Lingor, P."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Michel, U."],["dc.date.accessioned","2017-09-07T11:43:25Z"],["dc.date.available","2017-09-07T11:43:25Z"],["dc.date.issued","2011"],["dc.description.abstract","Repressor element-1 silencing transcription factor (REST) is a transcriptional repressor of neuron-specific genes that binds to a conserved DNA element, the neuron restrictive silencer element (NRSE/RE1). Interestingly, increased REST activity is found in several neurological diseases like Huntington's disease and cerebral ischemia. Recently, it was shown that NRSE dsRNA, a double-stranded non-coding RNA can bind to REST during a defined period of neuronal differentiation, and thereby changes REST from a transcriptional repressor to an activator of neuron-specific genes. Here, we analyzed the effects of NRSE dsRNA expression in primary retinal ganglion cells. We found that NRSE dsRNA expression vectors significantly enhance neurite outgrowth even when axonal degeneration is induced by neurotrophin deprivation. Transfection of HEK cells with NRSE dsRNA-expressing vectors altered their morphology leading to the formation of thin processes and induced the expression of neurofilament-68. Surprisingly, control vectors containing REST-binding sites, but not expressing NRSE dsRNA, resulted in the same effects, also in the retinal ganglion cell model. Reporter assays and retention of REST in the cytoplasm with a labeled NRSE/RE1-containing plasmid incapable of entering the nucleus suggest that sequestration of REST in the cytoplasm is the reason for the observed effects. No evidence for a biological function of NRSE dsRNA could be found in these models. We conclude that sequestration of REST leads to enhanced neurite outgrowth in retinal ganglion cells and that an increased activity of REST, as it is found in several neurodegenerative diseases, can be effectively modulated by sequestration of REST with plasmids containing NRSE/RE1 sites."],["dc.identifier.doi","10.1111/j.1742-4658.2011.08269.x"],["dc.identifier.gro","3142674"],["dc.identifier.isi","000294810600024"],["dc.identifier.pmid","21790997"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/104"],["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","1742-464X"],["dc.title","Plasmids containing NRSE/RE1 sites enhance neurite outgrowth of retinal ganglion cells via sequestration of REST independent of NRSE dsRNA expression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1887"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Nature Protocols"],["dc.bibliographiccitation.lastpage","1896"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Knöferle, J."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Michel, U."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:43:17Z"],["dc.date.available","2017-09-07T11:43:17Z"],["dc.date.issued","2011"],["dc.description.abstract","In this protocol, we describe the imaging of single axons in the rat optic nerve in vivo. Axons are labeled through the intravitreal injection of adeno-associated viral vectors (AAVs) expressing a fluorophore (duration of the procedure similar to 1 h). Two weeks after intravitreal injection, the optic nerve is surgically exposed (duration similar to 1 h) and labeled axons are imaged with an epifluorescence microscope either for up to 8 h or repetitively on the following days. Additionally, intravitreal injection of calcium-sensitive dyes allows for imaging of intra-axonal calcium kinetics. This procedure enables the analysis of the morphological changes of degenerating axons in the optic nerve in different lesion paradigms, such as optic nerve crush, axotomy or pin lesion. Furthermore, the effects of pharmacological manipulations on axonal stability and axonal calcium kinetics in axons of the central nervous system can be studied in vivo."],["dc.identifier.doi","10.1038/nprot.2011.403"],["dc.identifier.gro","3142620"],["dc.identifier.isi","000298157100005"],["dc.identifier.pmid","22051801"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft (DFG)"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1754-2189"],["dc.title","Imaging of rat optic nerve axons in vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1225"],["dc.bibliographiccitation.journal","Cell Death and Disease"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Barski, E."],["dc.contributor.author","Michel, U."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:46:15Z"],["dc.date.available","2017-09-07T11:46:15Z"],["dc.date.issued","2014"],["dc.description.abstract","The Rho/ROCK/LIMK pathway is central for the mediation of repulsive environmental signals in the central nervous system. Several studies using pharmacological Rho-associated protein kinase (ROCK) inhibitors have shown positive effects on neurite regeneration and suggest additional pro-survival effects in neurons. However, as none of these drugs is completely target specific, it remains unclear how these effects are mediated and whether ROCK is really the most relevant target of the pathway. To answer these questions, we generated adeno-associated viral vectors to specifically downregulate ROCK2 and LIM domain kinase (LIMK)-1 in rat retinal ganglion cells (RGCs) in vitro and in vivo. We show here that specific knockdown of ROCK2 and LIMK1 equally enhanced neurite outgrowth of RGCs on inhibitory substrates and both induced substantial neuronal regeneration over distances of more than 5mm after rat optic nerve crush (ONC) in vivo. However, only knockdown of ROCK2 but not LIMK1 increased survival of RGCs after optic nerve axotomy. Moreover, knockdown of ROCK2 attenuated axonal degeneration of the proximal axon after ONC assessed by in vivo live imaging. Mechanistically, we demonstrate here that knockdown of ROCK2 resulted in decreased intraneuronal activity of calpain and caspase 3, whereas levels of pAkt and collapsin response mediator protein 2 and autophagic flux were increased. Taken together, our data characterize ROCK2 as a specific therapeutic target in neurodegenerative diseases and demonstrate new downstream effects of ROCK2 including axonal degeneration, apoptosis and autophagy."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.format.extent","12"],["dc.identifier.doi","10.1038/cddis.2014.191"],["dc.identifier.gro","3142130"],["dc.identifier.isi","000337229300025"],["dc.identifier.pmid","24832597"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10116"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4877"],["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","2041-4889"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.subject","Cell death in the nervous system; Cell signalling; Neurodegeneration; Regeneration and repair in the nervous system"],["dc.title","ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS"],["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","6064"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","6069"],["dc.bibliographiccitation.volume","107"],["dc.contributor.author","Knöferle, J."],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Ostendorf, T."],["dc.contributor.author","Michel, U."],["dc.contributor.author","Planchamp, V."],["dc.contributor.author","Vutova, P."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Stadelmann, C."],["dc.contributor.author","Brück, W."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:46:07Z"],["dc.date.available","2017-09-07T11:46:07Z"],["dc.date.issued","2010"],["dc.description.abstract","Axonal degeneration is an initial key step in traumatic and neurodegenerative CNS disorders. We established a unique in vivo epifluorescence imaging paradigm to characterize very early events in axonal degeneration in the rat optic nerve. Single retinal ganglion cell axons were visualized by AAV-mediated expression of dsRed and this allowed the quantification of postlesional acute axonal degeneration (AAD). EM analysis revealed severe structural alterations of the cytoskeleton, cytoplasmatic vacuolization, and the appearance of autophagosomes within the first hours after lesion. Inhibition of autophagy resulted in an attenuation of acute axonal degeneration. Furthermore, a rapid increase of intraaxonal calcium levels following crush lesion could be visualized using a calcium-sensitive dye. Application of calcium channel inhibitors prevented crush-induced calcium increase and markedly attenuated axonal degeneration, whereas application of a calcium ionophore aggravated the degenerative phenotype. We finally demonstrate that increased postlesional autophagy is calcium dependent and thus mechanistically link autophagy and intraaxonal calcium levels. Both processes are proposed to be major targets for the manipulation of axonal degeneration in future therapeutic settings."],["dc.identifier.doi","10.1073/pnas.0909794107"],["dc.identifier.gro","3142949"],["dc.identifier.isi","000276159500067"],["dc.identifier.pmid","20231460"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/409"],["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","0027-8424"],["dc.title","Mechanisms of acute axonal degeneration in the optic nerve 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","168"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","176"],["dc.bibliographiccitation.volume","51"],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Solis, G. P."],["dc.contributor.author","Bodrikov, V."],["dc.contributor.author","Michel, U."],["dc.contributor.author","Haralampieva, D."],["dc.contributor.author","Shypitsyna, A."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.contributor.author","Stuermer, C. A. O."],["dc.date.accessioned","2017-09-07T11:47:49Z"],["dc.date.available","2017-09-07T11:47:49Z"],["dc.date.issued","2013"],["dc.description.abstract","The ability of fish retinal ganglion cells (RGCs) to regenerate their axons was shown to require the re-expression and function of the two proteins reggie-1 and -2. RGCs in mammals fail to upregulate reggie expression and to regenerate axons after lesion suggesting the possibility that induced upregulation might promote regeneration. In the present study, RGCs in adult rats were induced to express reggie-1 by intravitreal injection of adeno-associated viral vectors (AAV2/1) expressing reggie-1 (AAV.R1-EGFP) 14d prior to optic nerve crush. Four weeks later, GAP-43-positive regenerating axons had crossed the lesion and grown into the nerve at significantly higher numbers and length (up to 5 mm) than the control transduced with AAV.EGFP. Consistently, after transduction with AAV.R1-EGFP as opposed to AAV.EGFP, primary RGCs in vitro grew long axons on chondroitin sulfate proteoglycan (CSPG) and Nogo-A, both glial cell-derived inhibitors of neurite growth, suggesting that reggie-1 can provide neurons with the ability to override inhibitors of neurite growth. This reggie-1-mediated enhancement of growth was reproduced in mouse hippocampal and N2a neurons which generated axons 40-60% longer than their control counterparts. This correlates with the reggie-l-dependent activation of Src and PI3 kinase (PI3K), of the Rho family GTPase Rac1 and downstream effectors such as cofilin. This increased growth also depends on TC10, the GTPase involved in cargo delivery to the growth cone. Thus, the upregulation of reggie-1 in mammalian neurons provides nerve cells with neuron-intrinsic properties required for axon growth and successful regeneration in the adult mammalian CNS. (C) 2012 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.nbd.2012.11.007"],["dc.identifier.gro","3142387"],["dc.identifier.isi","000314627100019"],["dc.identifier.pmid","23174179"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7719"],["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","0969-9961"],["dc.title","Upregulation of reggie-1/flotillin-2 promotes axon regeneration in the rat optic nerve in vivo and neurite growth in vitro"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","395"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","404"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Knöferle, J."],["dc.contributor.author","Ramljak, S."],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Asif, A. R."],["dc.contributor.author","Michel, U."],["dc.contributor.author","Wouters, F. S."],["dc.contributor.author","Heermann, S."],["dc.contributor.author","Krieglstein, K."],["dc.contributor.author","Zerr, I."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:46:02Z"],["dc.date.available","2017-09-07T11:46:02Z"],["dc.date.issued","2010"],["dc.description.abstract","Malfunction of the ubiquitin-proteasome system has been implicated as a causal factor in the pathogenesis of aggregation-related disorders, e.g. Parkinson's disease. We show here that Transforming growth factor-beta 1 (TGF-beta), a multifunctional cytokine and trophic factor for dopaminergic (DAergic) neurons modulates proteasome function in primary midbrain neurons. TGF-beta differentially inhibited proteasomal subactivities with a most pronounced time-dependent inhibition of the peptidyl-glutamyl peptide hydrolyzing-like and chymotrypsin-like subactivity. Regulation of proteasomal activity could be specifically quantified in the DAergic subpopulation. Protein blot analysis revealed an accumulation of ubiquitinated proteins after TGF-beta treatment. The identity of these enriched proteins was further analyzed by 2D-gel electrophoresis and mass spectrometry. We found epidermal fatty acid binding protein (EFABP) to be strongly increased and ubiquitinated after TGF-beta treatment and confirmed this finding by co-immunoprecipitation. While application of TGF-beta increased neurite regeneration in a scratch lesion model, downregulation of EFABP by siRNA significantly decreased this effect. We thus postulate that a differential regulation of proteasomal function, as demonstrated for TGF-beta, can result in an enrichment of proteins, such as EFABP, that mediate physiological functions, such as neurite regeneration. (C) 2010 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.nbd.2010.02.011"],["dc.identifier.gro","3142916"],["dc.identifier.isi","000277648200010"],["dc.identifier.pmid","20211260"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/373"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: DFG-Research Center for Molecular Physiology of the Brain"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1095-953X"],["dc.relation.issn","0969-9961"],["dc.title","TGF-beta 1 enhances neurite outgrowth via regulation of proteasome function and EFABP"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2810"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","2827"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Vahsen, Björn Friedhelm"],["dc.contributor.author","Ribas, Vinicius Toledo"],["dc.contributor.author","Sundermeyer, Jonas"],["dc.contributor.author","Boecker, Alexander"],["dc.contributor.author","Dambeck, Vivian"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Shomroni, Orr"],["dc.contributor.author","Caldi Gomes, Lucas"],["dc.contributor.author","Tatenhorst, Lars"],["dc.contributor.author","Barski, Elisabeth"],["dc.contributor.author","Roser, Anna-Elisa"],["dc.contributor.author","Michel, Uwe"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Salinas, Gabriela"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Koch, Jan Christoph"],["dc.contributor.author","Lingor, Paul"],["dc.date.accessioned","2020-12-10T18:09:42Z"],["dc.date.available","2020-12-10T18:09:42Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1038/s41418-020-0543-y"],["dc.identifier.eissn","1476-5403"],["dc.identifier.issn","1350-9047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73733"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","261"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","275"],["dc.bibliographiccitation.volume","134"],["dc.contributor.author","Challagundla, Malleswari"],["dc.contributor.author","Koch, Jan Christoph"],["dc.contributor.author","Ribas, Vinicius Toledo"],["dc.contributor.author","Michel, Uwe"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Ostendorf, Thomas"],["dc.contributor.author","Bradke, Frank"],["dc.contributor.author","Müller, H. W."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, Paul"],["dc.date.accessioned","2017-09-07T11:43:44Z"],["dc.date.available","2017-09-07T11:43:44Z"],["dc.date.issued","2015"],["dc.description.abstract","A lesion to the rat rubrospinal tract is a model for traumatic spinal cord lesions and results in atrophy of the red nucleus neurons, axonal dieback, and locomotor deficits. In this study, we used adeno-associated virus (AAV)-mediated over-expression of BAG1 and ROCK2-shRNA in the red nucleus to trace [by co-expression of enhanced green fluorescent protein (EGFP)] and treat the rubrospinal tract after unilateral dorsal hemisection. We investigated the effects of targeted gene therapy on neuronal survival, axonal sprouting of the rubrospinal tract, and motor recovery 12weeks after unilateral dorsal hemisection at Th-8 in rats. In addition to the evaluation of BAG1 and ROCK2 as therapeutic targets in spinal cord injury, we aimed to demonstrate the feasibility and the limits of an AAV-mediated protein over-expression versus AAV.shRNA-mediated down-regulation in this traumatic CNS lesion model. Our results demonstrate that BAG1 and ROCK2-shRNA both promote neuronal survival of red nucleus neurons and enhance axonal sprouting proximal to the lesion."],["dc.identifier.doi","10.1111/jnc.13102"],["dc.identifier.gro","3141874"],["dc.identifier.isi","000357598000008"],["dc.identifier.pmid","25807858"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2034"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1471-4159"],["dc.relation.issn","0022-3042"],["dc.title","AAV-mediated expression of BAG1 and ROCK2-shRNA promote neuronal survival and axonal sprouting in a rat model of rubrospinal tract injury"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]