Weishaupt, Jochen Hans

[["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","791"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","10"],["dc.contributor.affiliation","Ruf, Wolfgang P.; \t\t \r\n\t\t Department of Neurology, Ulm University, 89081 Ulm, Germany, wolfgang.ruf@uni-ulm.de"],["dc.contributor.affiliation","Freischmidt, Axel; \t\t \r\n\t\t Department of Neurology, Ulm University, 89081 Ulm, Germany, axel.freischmidt@uni-ulm.de\t\t \r\n\t\t German Center for Neurodegenerative Diseases (DNZE), 89081 Ulm, Germany, axel.freischmidt@uni-ulm.de"],["dc.contributor.affiliation","Grozdanov, Veselin; \t\t \r\n\t\t Department of Neurology, Ulm University, 89081 Ulm, Germany, veselin.grozdanov@uni-ulm.de"],["dc.contributor.affiliation","Roth, Valerie; \t\t \r\n\t\t Department of Neurology, Ulm University, 89081 Ulm, Germany, valerie.roth@christophorus-kliniken.de"],["dc.contributor.affiliation","Brockmann, Sarah J.; \t\t \r\n\t\t Department of Neurology, Ulm University, 89081 Ulm, Germany, sarah.brockmann@uni-ulm.de"],["dc.contributor.affiliation","Mollenhauer, Brit; \t\t \r\n\t\t Department of Neurology, Universitätsmedizin Göttingen and Paracelsus-Elena-Klinik, 34128 Kassel, Germany, brit.mollenhauer@paracelsus-kliniken.de"],["dc.contributor.affiliation","Martin, Dorothea; \t\t \r\n\t\t Department of Neurology, Technische Universität München, 80333 Munich, Germany, Dorothea.a.martin@gmail.com"],["dc.contributor.affiliation","Haslinger, Bernhard; \t\t \r\n\t\t Department of Neurology, Technische Universität München, 80333 Munich, Germany, bernhard.haslinger@tum.de"],["dc.contributor.affiliation","Fundel-Clemens, Katrin; \t\t \r\n\t\t Boehringer Ingelheim Pharma GmbH & Co. KG, Div. Research Department, 88400 Biberach, Germany, katrin.fundel-clemens@boehringer-ingelheim.com"],["dc.contributor.affiliation","Otto, Markus; \t\t \r\n\t\t Department of Neurology, Ulm University, 89081 Ulm, Germany, markus.otto@uni-ulm.de"],["dc.contributor.affiliation","Arnim, Christine von; \t\t \r\n\t\t Department of Geriatrics, Göttingen University, 37075 Göttingen, Germany, christine.arnim@med.uni-goettingen.de"],["dc.contributor.affiliation","Holzmann, Karlheinz; \t\t \r\n\t\t Genomics-Core Facility, Center for Biomedical Research, University Hospital Ulm, 89081 Ulm, Germany, karlheinz.holzmann@uni-ulm.de"],["dc.contributor.affiliation","Ludolph, Albert C.; \t\t \r\n\t\t Department of Neurology, Ulm University, 89081 Ulm, Germany, Albert.Ludolph@rku.de\t\t \r\n\t\t German Center for Neurodegenerative Diseases (DNZE), 89081 Ulm, Germany, Albert.Ludolph@rku.de"],["dc.contributor.affiliation","Weishaupt, Jochen H.; \t\t \r\n\t\t Institute for Neurodegeneration, Universitätsmedizin Mannheim, 68167 Mannheim, Germany, Jochen.Weishaupt@medma.uni-heidelberg.de"],["dc.contributor.affiliation","Danzer, Karin M.; \t\t \r\n\t\t Department of Neurology, Ulm University, 89081 Ulm, Germany, Karin.Danzer@uni-ulm.de"],["dc.contributor.author","Ruf, Wolfgang P."],["dc.contributor.author","Freischmidt, Axel"],["dc.contributor.author","Grozdanov, Veselin"],["dc.contributor.author","Roth, Valerie"],["dc.contributor.author","Brockmann, Sarah J."],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Martin, Dorothea"],["dc.contributor.author","Haslinger, Bernhard"],["dc.contributor.author","Fundel-Clemens, Katrin"],["dc.contributor.author","Danzer, Karin M."],["dc.contributor.author","Otto, Markus"],["dc.contributor.author","Arnim, Christine von"],["dc.contributor.author","Holzmann, Karlheinz"],["dc.contributor.author","Ludolph, Albert C."],["dc.contributor.author","Weishaupt, Jochen H."],["dc.date.accessioned","2021-06-01T09:42:32Z"],["dc.date.available","2021-06-01T09:42:32Z"],["dc.date.issued","2021"],["dc.date.updated","2022-02-09T13:21:12Z"],["dc.description.abstract","Accumulating evidence suggests that microRNAs (miRNAs) are a contributing factor to neurodegenerative diseases. Although altered miRNA profiles in serum or plasma have been reported for several neurodegenerative diseases, little is known about the interaction between dysregulated miRNAs and their protein binding partners. We found significant alterations of the miRNA abundance pattern in serum and in isolated serum-derived extracellular vesicles of Parkinson’s disease (PD) patients. The differential expression of miRNA in PD patients was more robust in serum than in isolated extracellular vesicles and could separate PD patients from healthy controls in an unsupervised approach to a high degree. We identified a novel protein interaction partner for the strongly dysregulated hsa-mir-4745-5p. Our study provides further evidence for the involvement of miRNAs and HNF4a in PD. The demonstration that miRNA-protein binding might mediate the pathologic effects of HNF4a both by direct binding to it and by binding to proteins regulated by it suggests a complex role for miRNAs in pathology beyond the dysregulation of transcription."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/cells10040791"],["dc.identifier.eissn","2073-4409"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85280"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.publisher","MDPI"],["dc.relation.eissn","2073-4409"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Protein Binding Partners of Dysregulated miRNAs in Parkinson’s Disease Serum"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","795"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","813"],["dc.bibliographiccitation.volume","125"],["dc.contributor.author","Wagner, J."],["dc.contributor.author","Ryazanov, S."],["dc.contributor.author","Leonov, A."],["dc.contributor.author","Levin, J."],["dc.contributor.author","Shi, S."],["dc.contributor.author","Schmidt, F."],["dc.contributor.author","Prix, C."],["dc.contributor.author","Pan-Montojo, F."],["dc.contributor.author","Bertsch, U."],["dc.contributor.author","Mitteregger-Kretzschmar, G."],["dc.contributor.author","Geissen, M."],["dc.contributor.author","Eiden, M."],["dc.contributor.author","Leidel, F."],["dc.contributor.author","Hirschberger, T."],["dc.contributor.author","Deeg, A. A."],["dc.contributor.author","Krauth, J. J."],["dc.contributor.author","Zinth, W."],["dc.contributor.author","Tavan, P."],["dc.contributor.author","Pilger, J."],["dc.contributor.author","Zweckstetter, M."],["dc.contributor.author","Frank, T."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Weishaupt, J. H."],["dc.contributor.author","Uhr, M."],["dc.contributor.author","Urlaub, H."],["dc.contributor.author","Teichmann, U."],["dc.contributor.author","Samwer, M."],["dc.contributor.author","Bötzel, K."],["dc.contributor.author","Groschup, M."],["dc.contributor.author","Kretzschmar, Hans"],["dc.contributor.author","Griesinger, C."],["dc.contributor.author","Giese, A."],["dc.date.accessioned","2017-09-07T11:47:41Z"],["dc.date.available","2017-09-07T11:47:41Z"],["dc.date.issued","2013"],["dc.description.abstract","In neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and prion diseases, deposits of aggregated disease-specific proteins are found. Oligomeric aggregates are presumed to be the key neurotoxic agent. Here we describe the novel oligomer modulator anle138b [3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole], an aggregation inhibitor we developed based on a systematic high-throughput screening campaign combined with medicinal chemistry optimization. In vitro, anle138b blocked the formation of pathological aggregates of prion protein (PrPSc) and of alpha-synuclein (alpha-syn), which is deposited in PD and other synucleinopathies such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Notably, anle138b strongly inhibited all prion strains tested including BSE-derived and human prions. Anle138b showed structure-dependent binding to pathological aggregates and strongly inhibited formation of pathological oligomers in vitro and in vivo both for prion protein and alpha-synuclein. Both in mouse models of prion disease and in three different PD mouse models, anle138b strongly inhibited oligomer accumulation, neuronal degeneration, and disease progression in vivo. Anle138b had no detectable toxicity at therapeutic doses and an excellent oral bioavailability and blood-brain-barrier penetration. Our findings indicate that oligomer modulators provide a new approach for disease-modifying therapy in these diseases, for which only symptomatic treatment is available so far. Moreover, our findings suggest that pathological oligomers in neurodegenerative diseases share structural features, although the main protein component is disease-specific, indicating that compounds such as anle138b that modulate oligomer formation by targeting structure-dependent epitopes can have a broad spectrum of activity in the treatment of different protein aggregation diseases."],["dc.identifier.doi","10.1007/s00401-013-1114-9"],["dc.identifier.gro","3142347"],["dc.identifier.isi","000319357900002"],["dc.identifier.pmid","23604588"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10301"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7275"],["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","0001-6322"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and 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","49"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","60"],["dc.bibliographiccitation.volume","194"],["dc.contributor.author","Krumova, P."],["dc.contributor.author","Meulmeester, E."],["dc.contributor.author","Garrido, M."],["dc.contributor.author","Tirard, M."],["dc.contributor.author","Hsiao, H.-H."],["dc.contributor.author","Bossis, G."],["dc.contributor.author","Urlaub, H."],["dc.contributor.author","Zweckstetter, M."],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Melchior, F."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Weishaupt, J. H."],["dc.date.accessioned","2017-09-07T11:44:07Z"],["dc.date.available","2017-09-07T11:44:07Z"],["dc.date.issued","2011"],["dc.description.abstract","Posttranslational modification of proteins by attachment of small ubiquitin-related modifier (SUMO) contributes to numerous cellular phenomena. Sumoylation sometimes creates and abolishes binding interfaces, but increasing evidence points to another role for sumoylation in promoting the solubility of aggregation-prone proteins. Using purified alpha-synuclein, an aggregation-prone protein implicated in Parkinson's disease that was previously reported to be sumoylated upon overexpression, we compared the aggregation kinetics of unmodified and modified alpha-synuclein. Whereas unmodified alpha-synuclein formed fibrils, modified alpha-synuclein remained soluble. The presence of as little as 10% sumoylated alpha-synuclein was sufficient to delay aggregation significantly in vitro. We mapped SUMO acceptor sites in alpha-synuclein and showed that simultaneous mutation of lysines 96 and 102 to arginine significantly impaired alpha-synuclein sumoylation in vitro and in cells. Importantly, this double mutant showed increased propensity for aggregation and cytotoxicity in a cell-based assay and increased cytotoxicity in dopaminergic neurons of the substantia nigra in vivo. These findings strongly support the model that sumoylation promotes protein solubility and suggest that defects in sumoylation may contribute to aggregation-induced diseases."],["dc.identifier.doi","10.1083/jcb.201010117"],["dc.identifier.gro","3142699"],["dc.identifier.isi","000292768200007"],["dc.identifier.pmid","21746851"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8032"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/132"],["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","0021-9525"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Sumoylation inhibits alpha-synuclein aggregation and toxicity"],["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.artnumber","e43963"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","PlosOne"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Zschüntzsch, Jana"],["dc.contributor.author","Steffens, Heinz"],["dc.contributor.author","Scheffel, Jörg"],["dc.contributor.author","Göricke, Bettina"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Le Meur, Karim"],["dc.contributor.author","Kirchhoff, Frank"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Schomburg, Eike D."],["dc.contributor.author","Neusch, Clemens"],["dc.date.accessioned","2019-07-09T11:53:39Z"],["dc.date.available","2019-07-09T11:53:39Z"],["dc.date.issued","2012"],["dc.description.abstract","Mutations in SOD1 cause hereditary variants of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS). Pathophysiology of the disease is non-cell-autonomous, with toxicity deriving also from glia. In particular, microglia contribute to disease progression. Methylene blue (MB) inhibits the effect of nitric oxide, which mediates microglial responses to injury. In vivo 2P-LSM imaging was performed in ALS-linked transgenic SOD1G93A mice to investigate the effect of MB on microglia-mediated inflammation in the spinal cord. Local superfusion of the lateral spinal cord with MB inhibited the microglial reaction directed at a laser-induced axon transection in control and SOD1G93A mice. In vitro, MB at high concentrations inhibited cytokine and chemokine release from microglia of control and advanced clinical SOD1G93A mice. Systemic MB-treatment of SOD1G93A mice at early preclinical stages significantly delayed disease onset and motor dysfunction. However, an increase of MB dose had no additional effect on disease progression; this was unexpected in view of the local anti-inflammatory effects. Furthermore, in vivo imaging of systemically MB-treated mice also showed no alterations of microglia activity in response to local lesions. Thus although systemic MB treatment had no effect on microgliosis, instead, its use revealed an important influence on motor neuron survival as indicated by an increased number of lumbar anterior horn neurons present at the time of disease onset. Thus, potentially beneficial effects of locally applied MB on inflammatory events contributing to disease progression could not be reproduced in SOD1G93A mice via systemic administration, whereas systemic MB application delayed disease onset via neuroprotection."],["dc.format.extent","13"],["dc.identifier.doi","10.1371/journal.phone.0043963"],["dc.identifier.fs","592827"],["dc.identifier.pmid","22952827"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7861"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60471"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Influence of Methylene Blue on Microglia-Induced Inflammation and Motor Neuron Degeneration in the SOD1G93A Model for ALS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1232"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Pharmaceuticals"],["dc.bibliographiccitation.lastpage","1240"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Liman, Jan"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Dietz, Gunnar P. H."],["dc.date.accessioned","2019-07-09T11:53:05Z"],["dc.date.available","2019-07-09T11:53:05Z"],["dc.date.issued","2010"],["dc.description.abstract","Cdk5 is essential for neuronal differentiation processes in the brain. Activation of Cdk5 requires the association with the mostly neuron-specific p35 or p39. Overactivation of CDK5 by cleavage of p35 into p25 is thought to be involved in neurodegenerative processes. Here, we have tested an approach to inhibit pathological Cdk5 activation with a Tat-linked dominant-negative fragment of p25. It reduced cell death induced by staurosporine and showed a tendency to alleviate manganese-induced cell death, while it did not protect against 6-OHDA toxicity. Our results suggest that the Tat technique is a suitable tool to inhibit dysregulated CDK5."],["dc.identifier.doi","10.3390/ph3041232"],["dc.identifier.fs","577416"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6877"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60337"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1424-8247"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Cell-Penetrating Fragments of the Cdk5 Regulatory Subunit Are Protective in Models of Neurodegeneration"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","469"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Experimental Medicine"],["dc.bibliographiccitation.lastpage","480"],["dc.bibliographiccitation.volume","212"],["dc.contributor.author","Gao, Liang"],["dc.contributor.author","Brenner, David"],["dc.contributor.author","Llorens-Bobadilla, Enric"],["dc.contributor.author","Saiz-Castro, Gonzalo"],["dc.contributor.author","Frank, Tobias"],["dc.contributor.author","Wieghofer, Peter"],["dc.contributor.author","Hill, Oliver"],["dc.contributor.author","Thiemann, Meinolf"],["dc.contributor.author","Karray, Saoussen"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Martin-Villalba, Ana"],["dc.date.accessioned","2018-11-07T09:58:39Z"],["dc.date.available","2018-11-07T09:58:39Z"],["dc.date.issued","2015"],["dc.description.abstract","Neuroinflammation is increasingly recognized as a hallmark of neurodegeneration. Activated central nervous system-resident microglia and infiltrating immune cells contribute to the degeneration of dopaminergic neurons (DNs). However, how the inflammatory process leads to neuron loss and whether blocking this response would be beneficial to disease progression remains largely unknown. CD95 is a mediator of inflammation that has also been proposed as an apoptosis inducer in DNs, but previous studies using ubiquitous deletion of CD95 or CD95L in mouse models of neurodegeneration have generated conflicting results. Here we examine the role of CD95 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-induced neurodegeneration using tissue-specific deletion of CD95 or CD95L. We show that DN death is not mediated by CD95-induced apoptosis because deletion of CD95 in DNs does not influence MPTP-induced neurodegeneration. In contrast, deletion of CD95L in peripheral myeloid cells significantly protects against MPTP neurotoxicity and preserves striatal dopamine levels. Systemic pharmacological inhibition of CD95L dampens the peripheral innate response, reduces the accumulation of infiltrating myeloid cells, and efficiently prevents MPTP-induced DN death. Altogether, this study emphasizes the role of the peripheral innate immune response in neurodegeneration and identifies CD95 as potential pharmacological target for neurodegenerative disease."],["dc.description.sponsorship","DKFZ; Federal Ministry of Education and Research [BioRN-INB-07]"],["dc.identifier.doi","10.1084/jem.20132423"],["dc.identifier.isi","000352281000004"],["dc.identifier.pmid","25779632"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13818"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37408"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Rockefeller Univ Press"],["dc.relation.issn","1540-9538"],["dc.relation.issn","0022-1007"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.title","Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","695"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","713"],["dc.bibliographiccitation.volume","129"],["dc.contributor.author","Kunadt, Marcel"],["dc.contributor.author","Eckermann, Katrin"],["dc.contributor.author","Stuendl, Anne"],["dc.contributor.author","Gong, Jing"],["dc.contributor.author","Russo, Belisa"],["dc.contributor.author","Strauss, Katrin"],["dc.contributor.author","Rai, Surya"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Falomir Lockhart, Lisandro"],["dc.contributor.author","Schwalbe, Martin"],["dc.contributor.author","Krumova, Petranka"],["dc.contributor.author","Oliveira, Luis M. A."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Levin, Johannes"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Geiss‐Friedlander, Ruth"],["dc.contributor.author","Ludolph, Albert C."],["dc.contributor.author","Freischmidt, Axel"],["dc.contributor.author","Feiler, Marisa S."],["dc.contributor.author","Danzer, Karin M."],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Jovin, Thomas M."],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Schneider, Anja"],["dc.date.accessioned","2017-09-07T11:44:25Z"],["dc.date.available","2017-09-07T11:44:25Z"],["dc.date.issued","2015"],["dc.description.abstract","Extracellular alpha-Synuclein has been implicated in interneuronal propagation of disease pathology in Parkinson's Disease. How alpha-Synuclein is released into the extracellular space is still unclear. Here, we show that alpha-Synuclein is present in extracellular vesicles in the central nervous system. We find that sorting of alpha-Synuclein in extracellular vesicles is regulated by sumoylation and that sumoylation acts as a sorting factor for targeting of both, cytosolic and transmembrane proteins, to extracellular vesicles. We provide evidence that the SUMO-dependent sorting utilizes the endosomal sorting complex required for transport (ESCRT) by interaction with phosphoinositols. Ubiquitination of cargo proteins is so far the only known determinant for ESCRT-dependent sorting into the extracellular vesicle pathway. Our study reveals a function of SUMO protein modification as a Ubiquitin-independent ESCRT sorting signal, regulating the extracellular vesicle release of alpha-Synuclein. We deciphered in detail the molecular mechanism which directs alpha-Synuclein into extracellular vesicles which is of highest relevance for the understanding of Parkinson's disease pathogenesis and progression at the molecular level. We furthermore propose that sumo-dependent sorting constitutes a mechanism with more general implications for cell biology."],["dc.identifier.doi","10.1007/s00401-015-1408-1"],["dc.identifier.gro","3141916"],["dc.identifier.isi","000352716500007"],["dc.identifier.pmid","25778619"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11731"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2500"],["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.eissn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Extracellular vesicle sorting of alpha-Synuclein is regulated by sumoylation"],["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.issue","10"],["dc.bibliographiccitation.journal","BMC Neuroscience"],["dc.contributor.author","Weishaupt, Jochen Hans"],["dc.contributor.author","Dietz, Gunnar"],["dc.contributor.author","Göricke, Bettina"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Frank, Tobias"],["dc.contributor.author","Schlachetzki, Johannes C. M."],["dc.contributor.author","Meuer, Katrin"],["dc.contributor.author","Rohde, Gundula"],["dc.contributor.author","Schneider, Armin"],["dc.date.accessioned","2019-07-10T08:13:27Z"],["dc.date.available","2019-07-10T08:13:27Z"],["dc.date.issued","2009"],["dc.description.abstract","Background: The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) plays a crucial role in controlling the number of neutrophil progenitor cells. Its function is mediated via the G-CSF receptor, which was recently found to be expressed also in the central nervous system. In addition, G-CSF provided neuroprotection in models of neuronal cell death. Here we used the retinal ganglion cell (RGC) axotomy model to compare effects of local and systemic application of neuroprotective molecules. Results: We found that the G-CSF receptor is robustly expressed by RGCs in vivo and in vitro. We thus evaluated G-CSF as a neuroprotectant for RGCs and found a dose-dependent neuroprotective effect of G-CSF on axotomized RGCs when given subcutaneously. As stem stell mobilization had previously been discussed as a possible contributor to the neuroprotective effects of G-CSF, we compared the local treatment of RGCs by injection of G-CSF into the vitreous body with systemic delivery by subcutaneous application. Both routes of application reduced retinal ganglion cell death to a comparable extent. Moreover, G-CSF enhanced the survival of immunopurified RGCs in vitro. Conclusion: We thus show that G-CSF neuroprotection is at least partially independent of potential systemic effects and provide further evidence that the clinically applicable G-CSF could become a treatment option for both neurodegenerative diseases and glaucoma"],["dc.identifier.fs","568091"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5954"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61250"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1471-2202"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Both systemic and local application of granulocyte-colony stimulating factor (G-CSF) is neuroprotective after retinal ganglion cell axotomy."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]