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","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","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","217"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","232"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Günther, R."],["dc.contributor.author","Suhr, M."],["dc.contributor.author","Jansen, J."],["dc.contributor.author","Balck, A."],["dc.contributor.author","Saal, K.-A."],["dc.contributor.author","Barski, E."],["dc.contributor.author","Nientied, T."],["dc.contributor.author","Götz, A. A."],["dc.contributor.author","Koch, J.-C."],["dc.contributor.author","Mueller, B. K."],["dc.contributor.author","Weishaupt, J. H."],["dc.contributor.author","Sereda, M. W."],["dc.contributor.author","Hanisch, U.-K."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:46:53Z"],["dc.date.available","2017-09-07T11:46:53Z"],["dc.date.issued","2014"],["dc.description.abstract","Disease progression in amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons (MN) and their axons, but is also influenced by neighboring cells such as astrocytes and microglial cells. The role of microglia in ALS is complex as it switches from an anti-inflammatory and neuroprotective phenotype in early disease to a proinflammatory and neurotoxic phenotype in later stages. Our previous studies in models of neurodegeneration identified rho kinase (ROCK) as a target, which can be manipulated to beneficially influence disease progression. Here, we examined the neuroprotective potential of the ROCK inhibitor Fasudil to target the central pathogenic features of ALS. Application of Fasudil to kainic acid-lesioned primary MN in vitro resulted in a strong prosurvival effect. In vivo, SOD1(G93A) mice benefited from oral treatment with Fasudil showing prolonged survival and improved motor function. These findings were correlated to an improved survival of motor neurons and a pronounced alteration of astroglial and microglial cell infiltration of the spinal cord under Fasudil treatment. Modeling a proinflammatory microglial phenotype by stimulation with LPS in vitro, Fasudil decreased the release of proinflammatory cytokines and chemokines TNF, Il6, CCL2, CCL3, and CCL5 while CXCL1 release was only transiently suppressed. In sciatic nerve motor axons, neuromuscular junction remodeling processes were increased. In conclusion, we provide preclinical and neurobiological evidence that inhibition of ROCK by the clinically approved small molecule inhibitor Fasudil may be a novel therapeutic approach in ALS combining both neuroprotection and immunomodulation for the cure of this devastating disease. GLIA 2014;62:217-232"],["dc.identifier.doi","10.1002/glia.22601"],["dc.identifier.gro","3142195"],["dc.identifier.isi","000328209300005"],["dc.identifier.pmid","24311453"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5588"],["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","1098-1136"],["dc.relation.issn","0894-1491"],["dc.title","Rho Kinase Inhibition Modulates Microglia Activation and Improves Survival in a Model of Amyotrophic Lateral Sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","427"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Molecular and Cellular Neuroscience"],["dc.bibliographiccitation.lastpage","437"],["dc.bibliographiccitation.volume","42"],["dc.contributor.author","Bermel, C."],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Planchamp, V."],["dc.contributor.author","Gillardon, F."],["dc.contributor.author","Weishaupt, J. H."],["dc.contributor.author","Dietz, G. P. H."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:46:47Z"],["dc.date.available","2017-09-07T11:46:47Z"],["dc.date.issued","2009"],["dc.description.abstract","CNS regeneration is limited by lesion-induced neuronal apoptosis and an environment inhibiting axonal elongation. Inhibition of ROCK has been previously shown to promote regeneration in retinal ganglion cells (RGC) whereas Cdk5 inhibition mainly promoted survival. Therefore, we have evaluated the effects of combined treatment with inhibitors of ROCK and Cdk5. We show that in vitro, the co-application of the Cdk5 inhibitor, Indolinone A, and the ROCK inhibitor, Y-27632, potentiated the survival-promoting effect of either substance alone. However, neurite outgrowth in vitro was promoted only by the presence of Y-27632, not by Indolinone A alone. In the ex vivo explant and the in vivo optic nerve crush model the combination of both inhibitors significantly increased neurite outgrowth at small distances, but this effect leveled off for longer neurites. In Summary, the combined treatment with the Cdk5 inhibitor Indolinone A and the ROCK inhibitor Y-27632 results in a strong additive effect on neuronal survival, but is not able to increase the regenerative response beyond the effect of the ROCK inhibitor. (C) 2009 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.mcn.2009.09.005"],["dc.identifier.gro","3143032"],["dc.identifier.isi","000272121000017"],["dc.identifier.pmid","19782753"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/501"],["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","1044-7431"],["dc.title","Combined inhibition of Cdk5 and ROCK additively increase cell survival, but not the regenerative response in regenerating 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","757"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","765"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Dietz, G. P. H."],["dc.contributor.author","Stockhausen (née Peters), K. V."],["dc.contributor.author","Dietz, B."],["dc.contributor.author","Falkenburger, B. H."],["dc.contributor.author","Valbuena, P."],["dc.contributor.author","Opazo, F."],["dc.contributor.author","Lingor, P."],["dc.contributor.author","Meuer, K."],["dc.contributor.author","Weishaupt, J. H."],["dc.contributor.author","Schulz, J. B."],["dc.contributor.author","Bähr, M."],["dc.date.accessioned","2017-09-07T11:48:48Z"],["dc.date.available","2017-09-07T11:48:48Z"],["dc.date.issued","2008"],["dc.description.abstract","The anti-apoptotic Bcl-x(L) is a promising agent to prevent neurodegeneration in Parkinson's disease, which is characterized by a demise of dopaminergic neurons. We linked Bcl-x(L) to a peptide that allows its delivery across biological membranes and the blood-brain barrier. We tested the fusion protein in two models of Parkinson's Disease. Cell-permeable Bcl-x(L) protected neuroblastoma cells from the selective neurotoxin 1-methyl-4-phenylpyridinium. Furthermore, its systemic application in aged mice protected dopaminergic neurons following administration of MPTP as revealed by counting of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta. Hence, we present that a cell-permeable form of an anti-apoptotic protein can be delivered to CNS neurons through its systemic application, and we provide the proof that the delivery of this protein to the CNS neurons effectively prevents neuronal cell death in models of chronic neurodegenerative diseases."],["dc.identifier.doi","10.1111/j.1471-4159.2007.05028.x"],["dc.identifier.gro","3143353"],["dc.identifier.isi","000252322600015"],["dc.identifier.pmid","17995935"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/858"],["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","0022-3042"],["dc.title","Membrane-permeable Bcl-x(L) prevents MPTP-induced dopaminergic neuronal loss in the substantia nigra"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","675"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","686"],["dc.bibliographiccitation.volume","97"],["dc.contributor.author","Meuer, Katrin"],["dc.contributor.author","Pitzer, Claudia"],["dc.contributor.author","Teismann, Peter"],["dc.contributor.author","Krüger, Carola"],["dc.contributor.author","Göricke, Bettina"],["dc.contributor.author","Laage, Rico"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Peters, Kerstin"],["dc.contributor.author","Schlachetzki, Johannes C. M."],["dc.contributor.author","Kobayashi, Kazuto"],["dc.contributor.author","Dietz, Gunnar P. H."],["dc.contributor.author","Weber, Daniela"],["dc.contributor.author","Ferger, Boris"],["dc.contributor.author","Schäbitz, Wolf-Rüdiger"],["dc.contributor.author","Bach, Alfred"],["dc.contributor.author","Schulz, Jörg B."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Schneider, Armin"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.date.accessioned","2017-09-07T11:53:06Z"],["dc.date.available","2017-09-07T11:53:06Z"],["dc.date.issued","2006"],["dc.description.abstract","We have recently shown that the hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) is neuroprotective in rodent stroke models, and that this action appears to be mediated via a neuronal G-CSF receptor. Here, we report that the G-CSF receptor is expressed in rodent dopaminergic substantia nigra neurons, suggesting that G-CSF might be neuroprotective for dopaminergic neurons and a candidate molecule for the treatment of Parkinson's disease. Thus, we investigated protective effects of G-CSF in 1-methyl-4-phenylpyridinium (MPP+)-challenged PC12 cells and primary neuronal midbrain cultures, as well as in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Substantial protection was found against MPP+-induced dopaminergic cell death in vitro. Moreover, subcutaneous application of G-CSF at a dose of 40 mu g/Kg body weight daily over 13 days rescued dopaminergic substantia nigra neurons from MPTP-induced death in aged mice, as shown by quantification of tyrosine hydroxylase-positive substantia nigra cells. Using HPLC, a corresponding reduction in striatal dopamine depletion after MPTP application was observed in G-CSF-treated mice. Thus our data suggest that G-CSF is a novel therapeutic opportunity for the treatment of Parkinson's disease, because it is well-tolerated and already approved for the treatment of neutropenic conditions in humans."],["dc.identifier.doi","10.1111/j.1471-4159.2006.03727.x"],["dc.identifier.gro","3143697"],["dc.identifier.isi","000236798600007"],["dc.identifier.pmid","16573658"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1240"],["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","0022-3042"],["dc.title","Granulocyte-colony stimulating factor is neuroprotective 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"]]