Wouters, Fred Silvester

[["dc.bibliographiccitation.firstpage","551"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Alzheimer's Disease"],["dc.bibliographiccitation.lastpage","565"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Schmitz, M."],["dc.contributor.author","Wulf, K."],["dc.contributor.author","Signore, S. C."],["dc.contributor.author","Schulz-Schaeffer, W. J."],["dc.contributor.author","Kermer, P."],["dc.contributor.author","Baehr, M."],["dc.contributor.author","Wouters, F. S."],["dc.contributor.author","Zafar, S."],["dc.contributor.author","Zerr, I."],["dc.date.accessioned","2017-09-07T11:46:57Z"],["dc.date.available","2017-09-07T11:46:57Z"],["dc.date.issued","2014"],["dc.description.abstract","Previous studies indicate an important role for the cellular prion protein (PrPC) in the development of Alzheimer's disease (AD) pathology. In the present study, we analyzed the involvement of PrPC in different pathological mechanisms underlying AD: the processing of the amyloid-beta protein precursor (A beta PP) and its interaction with A beta PP, tau, and different phosphorylated forms of the tau protein (p-tau). The effect of PrPC on tau expression was investigated in various cellular compartments using a HEK293 cell model expressing a tau mutant (3PO-tau) or wild type (WT)-tau. We could show that PrPC reduces A beta PP cleavage, leading to decreased levels of A beta(40) and sA beta PP without changing the protein expression of A beta PP, beta-secretase, or gamma-secretase. Tau and its phosphorylated forms were identified as interactions partners for PrPC, raising the question as to whether PrPC might also be involved in tau pathology. Overexpression of PrPC in PRNP and 3PO-tau transfected cells resulted in a reduction of 3PO-tau and p-tau as well as a decrease of 3PO-tau-related toxicity. In addition, we used the transgenic PrPC knockout (Prnp0/0) mouse line to study the dynamics of tau phosphorylation, an important pathological hallmark in the pathogenesis of AD in vivo. There, an effect of PrPC on tau expression could be observed under oxidative stress conditions but not during aging. In summary, we provide further evidence for interactions of PrPC with proteins that are known to be the key players in AD pathogenesis. We identified tau and its phosphorylated forms as potential PrP-interactors and report a novel protective function of PrPC in AD-like tau pathology."],["dc.identifier.doi","10.3233/JAD-130566"],["dc.identifier.gro","3142228"],["dc.identifier.isi","000327598500009"],["dc.identifier.pmid","24028865"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10657"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5954"],["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.eissn","1875-8908"],["dc.relation.issn","1387-2877"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Impact of the Cellular Prion Protein on Amyloid-beta and 3PO-Tau Processing"],["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","521"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","531"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Esposito, Alessandro"],["dc.contributor.author","Dohm, Christoph P."],["dc.contributor.author","Kermer, Pawel"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Wouters, Fred S."],["dc.date.accessioned","2017-09-07T11:49:47Z"],["dc.date.available","2017-09-07T11:49:47Z"],["dc.date.issued","2007"],["dc.description.abstract","alpha-Synuclein is a primarily neuronal protein that is enriched at the presynapse. alpha-Synuclein and the microtubule binding protein tau have been implicated in neurodegenerative diseases. alpha-Synuclein is known to associate with phospholipid vesicles, regulates dopamine metabolism and exhibits chaperone activity, but its main role remains largely unknown. Furthermore, knowledge on its interactions and posttranslational modifications is essential for a molecular understanding of alpha-synucleinopathies. We investigated alpha-synuclein mutations, causative for autosomal dominant forms of Parkinson's disease (A30P, A53T and E46K), and phosphorylation mutants at serine 129 (S129A and S129D) using fluorescently labelled alpha-synuclein, actin and tau. The investigation of colocalizafion, and protein-protein interactions by Forster resonance energy transfer and fluorescence lifetime imaging showed that alpha-synuclein associates with the actin cytoskeleton and interacts with tau. The A30P mutation and cytoskeletal destabilization decreased this interaction. Given the concurrent loss of membrane binding by this mutation, we propose a membrane- bound functional complex with tau that might involve the actin cytoskeleton. (c) 2007 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.nbd.2007.01.014"],["dc.identifier.gro","3143496"],["dc.identifier.isi","000247146400003"],["dc.identifier.pmid","17408955"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1017"],["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","Alpha-synuclein and its disease-related mutants interact differentially with the microtubule protein tau and associate with the actin cytoskeleton"],["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","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Molecular Neuroscience"],["dc.bibliographiccitation.lastpage","8"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Dohm, Christoph P."],["dc.contributor.author","Siedenberg, Sandra"],["dc.contributor.author","Liman, Jan"],["dc.contributor.author","Esposito, Alessandro"],["dc.contributor.author","Wouters, Fred S."],["dc.contributor.author","Reed, John C."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Kermer, Pawel"],["dc.date.accessioned","2017-09-07T11:53:38Z"],["dc.date.available","2017-09-07T11:53:38Z"],["dc.date.issued","2006"],["dc.description.abstract","Bax ihibitor-1 (BI-1) has been characterized as an inhibitor of Bax-induced cell death in plants and various mammalian cell systems. To explore the function of BI-1 in neurons, we overexpressed BI-1 tagged to HA or GFP in rat nigral CSM14.1 and human SH-SY5Y neuroblastoma cells. Stable BI-1 expression proved marked protection from cell death induced by thapsigargine, a stress agent blocking the Call-ATPase of the endoplasmic reticulum (ER) but failed to inhibit cell death induced by staurosporine, a kinase inhibitor initiating mitochondria-dependent apoptosis. Moreover, BI-1 was neuroprotective in a paradigm mimicking ischemia, namely oxygen-glucose as well as serum deprivation. Examination of the subcellular distribution revealed that BI-1 predominantly locates to the ER and nuclear envelope but not mitochondria. Taken together, BI-1 overexpression in the ER is protective in neurons, making BI-1 an interesting target for future studies aiming at the inhibition of neuronal cell death during neurodegenerative diseases and stroke."],["dc.identifier.doi","10.1385/JMN:29:1:1"],["dc.identifier.gro","3143760"],["dc.identifier.isi","000237933400001"],["dc.identifier.pmid","16757804"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1309"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: NCI NIH HHS [CA67329]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0895-8696"],["dc.title","Bax inhibitor-1 protects neurons from oxygen-glucose deprivation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","505"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","513"],["dc.bibliographiccitation.volume","188"],["dc.contributor.author","Deeg, Sebastian"],["dc.contributor.author","Gralle, Mathias"],["dc.contributor.author","Sroka, Kamila"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Wouters, Fred Silvester"],["dc.contributor.author","Kermer, Pawel"],["dc.date.accessioned","2017-09-07T11:46:08Z"],["dc.date.available","2017-09-07T11:46:08Z"],["dc.date.issued","2010"],["dc.description.abstract","Mutations in the gene coding for DJ-1 protein lead to early-onset recessive forms of Parkinson's disease. It is believed that loss of DJ-1 function is causative for disease, although the function of DJ-1 still remains a matter of controversy. We show that DJ-1 is localized in the cytosol and is associated with membranes and organelles in the form of homodimers. The disease-related mutation L166P shifts its subcellular distribution to the nucleus and decreases its ability to dimerize, impairing cell survival. Using an intracellular foldase biosensor, we found that wild-type DJ-1 possesses chaperone activity, which is abolished by the L166P mutation. We observed that this aberrant phenotype can be reversed by the expression of the cochaperone BAG1 (Bcl-2-associated athanogene 1), restoring DJ-1 subcellular distribution, dimer formation, and chaperone activity and ameliorating cell survival."],["dc.identifier.doi","10.1083/jcb.200904103"],["dc.identifier.gro","3142963"],["dc.identifier.isi","000274723800009"],["dc.identifier.pmid","20156966"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6087"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/425"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft (DFG) [EXC171]"],["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","BAG1 restores formation of functional DJ-1 L166P dimers and DJ-1 chaperone activity"],["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","2"],["dc.bibliographiccitation.journal","Journal of Neural Transmission"],["dc.bibliographiccitation.volume","116"],["dc.contributor.author","Deeg, S."],["dc.contributor.author","Kermer, Pawel"],["dc.contributor.author","Sroka, K."],["dc.contributor.author","Wouters, F."],["dc.date.accessioned","2018-11-07T08:33:11Z"],["dc.date.available","2018-11-07T08:33:11Z"],["dc.date.issued","2009"],["dc.format.extent","228"],["dc.identifier.isi","000269823900031"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17515"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Wien"],["dc.relation.conference","6th German Parkinson Congress of the German-Parkinson-Society (DPG)"],["dc.relation.eventlocation","Marburg, GERMANY"],["dc.relation.issn","0300-9564"],["dc.title","BAG1 restores DJ-1 chaperone function and dimerisation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3715"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Molecular and Cellular Biology"],["dc.bibliographiccitation.lastpage","3725"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Liman, Jan"],["dc.contributor.author","Ganesan, Sundar"],["dc.contributor.author","Dohm, Christoph Peter"],["dc.contributor.author","Krajewski, S."],["dc.contributor.author","Reed, John C."],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Wouters, Fred S."],["dc.contributor.author","Kermer, Pawel"],["dc.date.accessioned","2017-09-07T11:54:30Z"],["dc.date.available","2017-09-07T11:54:30Z"],["dc.date.issued","2005"],["dc.description.abstract","It was recently shown that Bcl-2-associated athanogene 1 (BAG1) is a potent neuroprotectant as well as a marker of neuronal differentiation. Since there appears to exist an equilibrium within the cell between BAG1 binding to heat shock protein 70 (Hsp70) and BAG1 binding to Raf-1 kinase, we hypothesized that changing BAG1 binding characteristics might significantly alter BAG1 function. To this end, we compared rat CSM14.1 cells and human SHSY-5Y cells stably overexpressing full-length BAG1 or a deletion mutant (BAG Delta C) no longer capable of binding to Hsp70. Using a novel yellow fluorescent protein-based foldase biosensor, we demonstrated an upregulation of chaperone in situ activity in cells overexpressing full-length BAG1 but not in cells overexpressing BAG Delta C compared to wild-type cells. Interestingly, in contrast to the nuclear and cytosolic localizations of full-length BAG1, BAG Delta C was expressed exclusively in the cytosol. Furthermore, cells expressing BAG Delta C were no longer protected against cell death. However, they still showed accelerated neuronal differentiation. Together, these results suggest that BAG1-induced activation of Hsp70 is important for neuroprotectivity, while BAG1-dependent modulation of neuronal differentiation in vitro is not."],["dc.identifier.doi","10.1128/MCB.25.9.3715-3725.2005"],["dc.identifier.gro","3143862"],["dc.identifier.isi","000228679300030"],["dc.identifier.pmid","15831476"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1422"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: NCI NIH HHS [R01 CA067329, CA 67329]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0270-7306"],["dc.title","Interaction of BAG1 and Hsp70 mediates neuroprotectivity and increases chaperone activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neural Transmission"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Dohm, C. P."],["dc.contributor.author","Esposito, Alessandro"],["dc.contributor.author","Liman, Jan"],["dc.contributor.author","Reed, J. C."],["dc.contributor.author","Wouters, Fred S."],["dc.contributor.author","Baehr, M."],["dc.contributor.author","Kermer, Pawel"],["dc.date.accessioned","2018-11-07T11:04:36Z"],["dc.date.available","2018-11-07T11:04:36Z"],["dc.date.issued","2007"],["dc.format.extent","X"],["dc.identifier.isi","000244485200047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51879"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Wien"],["dc.relation.conference","5th Congress Deutsche-Parkinson-Gesellschaft"],["dc.relation.eventlocation","Ulm, GERMANY"],["dc.relation.issn","0300-9564"],["dc.title","Molecular mechanisms and neuroprotection in cellular models of Parkinson's disease"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]