Weishaupt, Jochen Hans

[["dc.bibliographiccitation.firstpage","651"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","661"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Meuer, K."],["dc.contributor.author","Suppanz, I. E."],["dc.contributor.author","Lingor, P."],["dc.contributor.author","Planchamp, V."],["dc.contributor.author","Göricke, B."],["dc.contributor.author","Fichtner, L."],["dc.contributor.author","Braus, G. H."],["dc.contributor.author","Dietz, G. P. H."],["dc.contributor.author","Jakobs, S."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Weishaupt, J. H."],["dc.date.accessioned","2017-09-07T11:49:50Z"],["dc.date.available","2017-09-07T11:49:50Z"],["dc.date.issued","2007"],["dc.description.abstract","Under physiological conditions, mitochondrial morphology dynamically shifts between a punctuate appearance and tubular networks. However, little is known about upstream signal transduction pathways that regulate mitochondrial morphology. We show that mitochondrial fission is a very early and kinetically invariant event during neuronal cell death, which causally contributes to cytochrome c release and neuronal apoptosis. Using a small molecule CDK5 inhibitor, as well as a dominant-negative CDK5 mutant and RNAi knockdown experiments, we identified CDK5 as an upstream signalling kinase that regulates mitochondrial fission during apoptosis of neurons. Vice versa, our study shows that mitochondrial fission is a modulator contributing to CDK5-mediated neurotoxicity. Thereby, we provide a link that allows integration of CDK5 into established neuronal apoptosis pathways."],["dc.identifier.doi","10.1038/sj.cdd.4402087"],["dc.identifier.gro","3143515"],["dc.identifier.isi","000245102900002"],["dc.identifier.pmid","17218957"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1038"],["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","1350-9047"],["dc.title","Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","17"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Molecular Neuroscience"],["dc.bibliographiccitation.lastpage","25"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Klocker, N."],["dc.contributor.author","Bähr, Mathias"],["dc.date.accessioned","2017-09-07T11:43:03Z"],["dc.date.available","2017-09-07T11:43:03Z"],["dc.date.issued","2005"],["dc.description.abstract","It has been proposed that neurons being exposed to proapoptotic stimuli undergo dedifferentiation, a process that can either allow for regeneration and axon regrowth or, if remaining incomplete, can force the cell to activate apoptotic pathways. A pivotal step in the differentiation program from neuronal precursor cells to differentiated, postmitotic neurons is their exit from the cell cycle. The POU domain transcription factors Brn-3b and Brn-3a, which are expressed in retinal ganglion cells (RGCs) directly after the exit of RGC precursors from the cell cycle, can be employed as RGC-specific differentiation markers to study potential dedifferentiation of RGCs after axotomy. Here, we examined mRNA and protein expression of Brn-3a and -3b in rat RGCs following axonal lesion. We observed a rapid down-regulation of Brn-3a and -3b protein expression in axotomized RGCs, clearly preceding apoptosis of RGCs. Using real-time PCR, we show that regulation of Brn-3 expression occurred at the transcriptional level. The small subset of RGCs regenerating into a peripheral nerve graft did not (re-)express Brn-3a or -b. In conclusion, we found further evidence supporting the hypothesis of a dedifferentiation process in severed mature neurons. As Brn-3b expression has been shown to be a prerequisite for developmental survival of most RGCs and Brn-3a activates transcription of anti-apoptotic genes, down-regulation of Brn-3 transcription factors might be causally involved in the secondary death of adult RGCs following axotomy."],["dc.identifier.doi","10.1385/JMN:26:1:017"],["dc.identifier.gro","3143913"],["dc.identifier.isi","000230412700002"],["dc.identifier.pmid","15968082"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1480"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0895-8696"],["dc.title","Axotomy-induced early down-regulation of POU-IV class transcription factors Brn-3a and Brn-3b in retinal ganglion cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1516"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Neurology"],["dc.bibliographiccitation.lastpage","1525"],["dc.bibliographiccitation.volume","266"],["dc.contributor.author","Dorst, Johannes"],["dc.contributor.author","Chen, Lu"],["dc.contributor.author","Rosenbohm, Angela"],["dc.contributor.author","Dreyhaupt, Jens"],["dc.contributor.author","Hübers, Annemarie"],["dc.contributor.author","Schuster, Joachim"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Kassubek, Jan"],["dc.contributor.author","Gess, Burkhard"],["dc.contributor.author","Meyer, Thomas"],["dc.contributor.author","Weyen, Ute"],["dc.contributor.author","Hermann, Andreas"],["dc.contributor.author","Winkler, Jürgen"],["dc.contributor.author","Grehl, Torsten"],["dc.contributor.author","Hagenacker, Tim"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Koch, Jan C."],["dc.contributor.author","Sperfeld, Anne"],["dc.contributor.author","Petri, Susanne"],["dc.contributor.author","Großkreutz, Julian"],["dc.contributor.author","Metelmann, Moritz"],["dc.contributor.author","Wolf, Joachim"],["dc.contributor.author","Winkler, Andrea S."],["dc.contributor.author","Klopstock, Thomas"],["dc.contributor.author","Boentert, Matthias"],["dc.contributor.author","Johannesen, Siw"],["dc.contributor.author","Storch, Alexander"],["dc.contributor.author","Schrank, Bertold"],["dc.contributor.author","Zeller, Daniel"],["dc.contributor.author","Liu, Xiao-lu"],["dc.contributor.author","Tang, Lu"],["dc.contributor.author","Fan, Dong-Sheng"],["dc.contributor.author","Ludolph, Albert C."],["dc.date.accessioned","2020-12-10T14:10:33Z"],["dc.date.available","2020-12-10T14:10:33Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s00415-019-09290-4"],["dc.identifier.eissn","1432-1459"],["dc.identifier.issn","0340-5354"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70799"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Prognostic factors in ALS: a comparison between Germany and China"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1013"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","1023"],["dc.bibliographiccitation.volume","129"],["dc.contributor.author","Liman, Jan"],["dc.contributor.author","Deeg, S."],["dc.contributor.author","Voigt, A."],["dc.contributor.author","Voßfeldt, H."],["dc.contributor.author","Dohm, C. P."],["dc.contributor.author","Karch, A."],["dc.contributor.author","Weishaupt, Jochen"],["dc.contributor.author","Schulz, J. B."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Kermer, P."],["dc.date.accessioned","2017-09-07T11:46:13Z"],["dc.date.available","2017-09-07T11:46:13Z"],["dc.date.issued","2014"],["dc.description.abstract","Spinocerebellar ataxia type 3 (SCA3) is one of at least nine inherited neurodegenerative diseases caused by an expansion of a polyglutamine tract within corresponding disease-specific proteins. In case of SCA3, mutation of Ataxin-3 results in aggregation of misfolded protein, formation of intranuclear as well as cytosolic inclusion bodies and cell death in distinct neuronal populations. Since cyclin-dependent kinase-5 (CDK5) has been shown to exert beneficial effects on aggregate formation and cell death in various polyglutamine diseases, we tested its therapeutic potential for SCA3. Our data show increased caspase-dependent Ataxin-3 cleavage, aggregation, and neurodegeneration in the absence of sufficient CDK5 activity. This disease-propagating effect could be reversed by mutation of the caspase cleavage site in Ataxin-3. Moreover, reduction of CDK5 expression levels by RNAi in vivo enhances SCA3 toxicity as assayed in a Drosophila model for SCA3. In summary, we present CDK5 as a potent neuroprotectant, regulating cleavage and thereby toxicity of Ataxin-3 and other polyglutamine proteins. We propose that increased caspase-dependent cleavage of mutated Ataxin-3, because of missing CDK5 shielding, leads to aggregation and cell death. Moreover, reduction of CDK5 expression levels by RNAi in vivo enhances SCA3 toxicity as assayed in a Drosophila model for SCA3. We think that CDK5 functions as a shield against cleavage-induced toxification and thereby is an interesting target for therapeutic intervention in polyQ disease in general."],["dc.identifier.doi","10.1111/jnc.12684"],["dc.identifier.gro","3142111"],["dc.identifier.isi","000337760500011"],["dc.identifier.pmid","24548080"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4666"],["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","1471-4159"],["dc.relation.issn","0022-3042"],["dc.title","CDK5 protects from caspase-induced Ataxin-3 cleavage and neurodegeneration"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3355"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","3370"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Frank, T."],["dc.contributor.author","Tatenhorst, L."],["dc.contributor.author","Saal, K. A."],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","Szego, E. M."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Weishaupt, J. H."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:48:22Z"],["dc.date.available","2017-09-07T11:48:22Z"],["dc.date.issued","2012"],["dc.description.abstract","Axonal degeneration is one of the earliest features of Parkinson's disease pathology, which is followed by neuronal death in the substantia nigra and other parts of the brain. Inhibition of axonal degeneration combined with cellular neuroprotection therefore seem key to targeting an early stage in Parkinson's disease progression. Based on our previous studies in traumatic and neurodegenerative disease models, we have identified rho kinase as a molecular target that can be manipulated to disinhibit axonal regeneration and improve survival of lesioned central nervous system neurons. In this study, we examined the neuroprotective potential of pharmacological rho kinase inhibition mediated by fasudil in the in vitro 1-methyl-4-phenylpyridinium cell culture model and in the subchronic in vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Application of fasudil resulted in a significant attenuation of dopaminergic cell loss in both paradigms. Furthermore, dopaminergic terminals were preserved as demonstrated by analysis of neurite network in vitro, striatal fibre density and by neurochemical analysis of the levels of dopamine and its metabolites in the striatum. Behavioural tests demonstrated a clear improvement in motor performance after fasudil treatment. The Akt survival pathway was identified as an important molecular mediator for neuroprotective effects of rho kinase inhibition in our paradigm. We conclude that inhibition of rho kinase using the clinically approved small molecule inhibitor fasudil may be a promising new therapeutic strategy for Parkinson's disease."],["dc.identifier.doi","10.1093/brain/aws254"],["dc.identifier.gro","3142444"],["dc.identifier.isi","000311644800021"],["dc.identifier.pmid","23087045"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9499"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8352"],["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","0006-8950"],["dc.rights","CC BY-NC 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/3.0"],["dc.title","Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson's disease"],["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","186"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Pineal Research"],["dc.bibliographiccitation.lastpage","187"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Jacob, Sonja"],["dc.contributor.author","Poeggeler, Burkhard"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Sirén, Anna-Leena"],["dc.contributor.author","Hardeland, Rüdiger"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:45:41Z"],["dc.date.available","2017-09-07T11:45:41Z"],["dc.date.issued","2002"],["dc.identifier.doi","10.1034/j.1600-079X.2002.02943.x"],["dc.identifier.gro","3150431"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7194"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.issn","0742-3098"],["dc.title","Melatonin as a candidate compound for neuroprotection in amyotrophic lateral sclerosis (ALS): high tolerability of daily oral melatonin administration in ALS patients"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1914"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","1925"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Frank, T."],["dc.contributor.author","Klinker, F."],["dc.contributor.author","Falkenburger, B. H."],["dc.contributor.author","Laage, R."],["dc.contributor.author","Lühder, F."],["dc.contributor.author","Göricke, B."],["dc.contributor.author","Schneider, A."],["dc.contributor.author","Neurath, H."],["dc.contributor.author","Desel, H."],["dc.contributor.author","Liebetanz, D."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Weishaupt, J. H."],["dc.date.accessioned","2017-09-07T11:48:52Z"],["dc.date.available","2017-09-07T11:48:52Z"],["dc.date.issued","2012"],["dc.description.abstract","Recent proof-of-principle data showed that the haematopoietic growth factor granulocyte colony-stimulating factor (filgrastim) mediates neuroprotection in rodent models of Parkinson's disease. In preparation for future clinical trials, we performed a preclinical characterization of a pegylated derivative of granulocyte colony-stimulating factor (pegfilgrastim) in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. We determined serum and cerebrospinal fluid drug levels after subcutaneous injection. A single injection of pegfilgrastim was shown to achieve stable levels of granulocyte colony-stimulating factor in both serum and cerebrospinal fluid with substantially higher levels compared to repetitive filgrastim injections. Leucocyte blood counts were only transiently increased after repeated injections. We demonstrated substantial dose-dependent long-term neuroprotection by pegfilgrastim in both young and aged mice, using bodyweight-adjusted doses that are applicable in clinical settings. Importantly, we found evidence for the functionally relevant preservation of nigrostriatal projections by pegfilgrastim in our model of Parkinson's disease, which resulted in improved motor performance. The more stable levels of pegylated neuroprotective proteins in serum and cerebrospinal fluid may represent a general advantage in the treatment of chronic neurodegenerative diseases and the resulting longer injection intervals are likely to improve patient compliance. In summary, we found that pegylation of a neuroprotective growth factor improved its pharmacokinetic profile over its non-modified counterpart in an in vivo model of Parkinson's disease. As the clinical safety profile of pegfilgrastim is already established, these data suggest that evaluation of pegfilgrastim in further Parkinson's disease models and ultimately clinical feasibility studies are warranted."],["dc.identifier.doi","10.1093/brain/aws054"],["dc.identifier.gro","3142529"],["dc.identifier.isi","000304538900022"],["dc.identifier.pmid","22427327"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8890"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Michael J. Fox Foundation"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0006-8950"],["dc.subject","granulocyte colony-stimulating factor; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; neuroprotection; Parkinson’s disease"],["dc.title","Pegylated granulocyte colony-stimulating factor conveys long-term neuroprotection and improves functional outcome in a model of Parkinson's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","312"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.bibliographiccitation.lastpage","321"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Ganesan, S."],["dc.contributor.author","Rohde, G."],["dc.contributor.author","Eckermann, K."],["dc.contributor.author","Sroka, K."],["dc.contributor.author","Schaefer, M. K. E."],["dc.contributor.author","Dohm, C. P."],["dc.contributor.author","Kermer, P."],["dc.contributor.author","Haase, G."],["dc.contributor.author","Wouters, F."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Weishaupt, J. H."],["dc.date.accessioned","2017-09-07T11:48:47Z"],["dc.date.available","2017-09-07T11:48:47Z"],["dc.date.issued","2008"],["dc.description.abstract","Mutant superoxide dismutase 1 (mtSOD1) causes dominantly inherited amyotrophic lateral sclerosis (ALS). The mechanism for mtSOD1 toxicity remains unknown. Two main hypotheses are the impairment of proteasomal function and chaperone depletion by misfolded mtSOD1. Here, we employed FRET/FLIM and biosensor imaging to quantitatively localize ubiquitination, as well as chaperone binding of mtSOD1, and to assess their effect on proteasomal and protein folding activities. We found large differences in ubiquitination and chaperone interaction levels for wild-type (wt) SOD1 versus mtSOD1 in intact single cells. Moreover, SOD1 ubiquitination levels differ between proteasomal structures and cytoplasmic material. Hsp70 binding and ubiquitination of wt and mtSOD1 species are highly correlated, demonstrating the coupled upregulation of both cellular detoxification mechanisms upon mtSOD1 expression. Biosensor imaging in single cells revealed that mtSOD1 expression alters cellular protein folding activity but not proteasomal function in the neuronal cell line examined. Our results provide the first cell-bycell- analysis of SOD1 ubiquitination and chaperone interaction. Moreover, our study opens new methodological avenues for cell biological research on ALS."],["dc.identifier.doi","10.1038/sj.cdd.4402262"],["dc.identifier.gro","3143350"],["dc.identifier.isi","000252387900011"],["dc.identifier.pmid","17992192"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/854"],["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","1350-9047"],["dc.title","Mutant SOD1 detoxification mechanisms in intact single cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","598"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Neuroradiology"],["dc.bibliographiccitation.lastpage","600"],["dc.contributor.author","Jacob, Sonja"],["dc.contributor.author","Finsterbusch, J."],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Khorram-Sefat, D."],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:45:43Z"],["dc.date.available","2017-09-07T11:45:43Z"],["dc.date.issued","2003"],["dc.description.abstract","Amyotrophic lateral sclerosis (ALS) is a predominantly clinical and electromyographic diagnosis. Conventional MRI reveals atrophy of the motor system, particularly the pyramidal tract, in the advanced stages but does not provide a sensitive measure of disease progression. Three patients with different principal symptoms of ALS, i.e., with predominant involvement of the upper (UMN) or lower (UMN) motor neurons, or bulbar disease, respectively, underwent serial clinical examination including lung function tests, conventional MRI, and diffusion tensor imaging (DTI). MRI demonstrated changes in of the pyramidal tract without measurable variation on follow-up. The patient with UMN involvement showed remarkable progressive loss of diffusion anisotropy in the pyramidal tract. DTI might be useful, together with clinical follow-up, as an objective morphological marker in therapeutic trials."],["dc.identifier.doi","10.1007/s00234-003-1014-0"],["dc.identifier.gro","3150437"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7201"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.relation.issn","0028-3940"],["dc.title","Diffusion tensor imaging for long-term follow-up of corticospinal tract degeneration in amyotrophic lateral sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1514"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Investigative Ophthalmology & Visual Science"],["dc.bibliographiccitation.lastpage","1522"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Rohde, Gundula"],["dc.contributor.author","Pölking, Esther"],["dc.contributor.author","Sirén, Anna-Leena"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Bähr, Mathias"],["dc.date.accessioned","2017-09-07T11:43:24Z"],["dc.date.available","2017-09-07T11:43:24Z"],["dc.date.issued","2004"],["dc.description.abstract","Purpose. Erythropoietin (EPO) modulates erythropoiesis by inhibiting apoptosis in erythrocyte progenitors. Recently, EPO has been shown to be protective in experimental models of mechanical trauma, neuroinflammation, cerebral and retinal ischemia, and even in a human stroke trial. However, little is known about EPO signal transduction in vivo and the usefulness of EPO in the prevention of the chronic, purely apoptotic neuronal cell death that contributes to vision loss in glaucoma and the progression of neurodegenerative diseases. Methods. EPO's effects and signaling in the retinal ganglion cell axotomy paradigm were studied by Western blot analysis and immunohistochemistry, receptor expression was characterized in the retina before and after lesion. EPO was injected into the vitreous body to investigate neuroprotection of axotomized rat RGCs. Moreover, EPO's effects were studied in cultures of immunopurified retinal ganglion cells. Signal-transduction pathways transmitting neuroprotective EPO effects in vivo were characterized by the use of specific kinase inhibitors, immunohistochemistry, and Western blot analysis. Results. EPO receptors (EPORs) were expressed on RGC somata and dendrites in vivo. EPOR expression did not significantly change after axotomy. Application of EPO prevented death of neurotrophic-factor-deprived immunopurified rat RGCs in vitro, rescued axotomized RGCs in vivo, and prevented caspase-3 activation. EPO-induced Akt phosphorylation and survival-promoting EPO effects were completely abolished by inhibition of PI-3-kinase. EPO neuroprotection followed a bell-shaped dose-response curve in vitro and in vivo, whereas toxic EPO effects were never observed, even at high concentrations. Conclusions. These data support a potential role for EPO as a therapeutic molecule against predominantly apoptotic neuronal cell death in the context of glaucoma or neurodegenerative diseases and delineate the PI-3-K/Akt pathway as the predominant mediator of EPO neuroprotection in this in vivo paradigm of neuronal cell death."],["dc.identifier.doi","10.1167/iovs.03-1039"],["dc.identifier.gro","3143992"],["dc.identifier.isi","000221084700034"],["dc.identifier.pmid","15111610"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1566"],["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.issn","0146-0404"],["dc.title","Effect of Erythropoietin Axotomy-Induced Apoptosis in Rat Retinal Ganglion Cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]