Szegő, Éva Mónica

[["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.artnumber","e28855"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Graeber, Simone"],["dc.contributor.author","Szego, Eva M."],["dc.contributor.author","Moisoi, Nicoleta"],["dc.contributor.author","Martins, L. Miguel"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Kermer, Pawel"],["dc.date.accessioned","2018-11-07T08:48:56Z"],["dc.date.available","2018-11-07T08:48:56Z"],["dc.date.issued","2011"],["dc.description.abstract","Heterozygous loss-of-function mutation of the human gene for the mitochondrial protease HtrA2 has been associated with increased risk to develop mitochondrial dysfunction, a process known to contribute to neurodegenerative disorders such as Huntington's disease (HD) and Parkinson's disease (PD). Knockout of HtrA2 in mice also leads to mitochondrial dysfunction and to phenotypes that resemble those found in neurodegenerative disorders and, ultimately, lead to death of animals around postnatal day 30. Here, we show that Idebenone, a synthetic antioxidant of the coenzyme Q family, and Resveratrol, a bioactive compound extracted from grapes, are both able to ameliorate this phenotype. Feeding HtrA2 knockout mice with either compound extends lifespan and delays worsening of the motor phenotype. Experiments conducted in cell culture and on brain tissue of mice revealed that each compound has a different mechanism of action. While Idebenone acts by downregulating the integrated stress response, Resveratrol acts by attenuating apoptosis at the level of Bax. These activities can account for the delay in neuronal degeneration in the striata of these mice and illustrate the potential of these compounds as effective therapeutic approaches against neurodegenerative disorders such as HD or PD."],["dc.identifier.doi","10.1371/journal.pone.0028855"],["dc.identifier.isi","000298665600012"],["dc.identifier.pmid","22205977"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7784"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21336"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Idebenone and Resveratrol Extend Lifespan and Improve Motor Function of HtrA2 Knockout 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.artnumber","UNSP 239"],["dc.bibliographiccitation.journal","Frontiers in Aging Neuroscience"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Tönges, L."],["dc.contributor.author","Szegö, E. M."],["dc.contributor.author","Hause, P."],["dc.contributor.author","Saal, K.-A."],["dc.contributor.author","Tatenhorst, L."],["dc.contributor.author","Koch, J. C."],["dc.contributor.author","D'Hedouville, Z."],["dc.contributor.author","Dambeck, V."],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Dohm, C. P."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Lingor, P."],["dc.date.accessioned","2017-09-07T11:45:32Z"],["dc.date.available","2017-09-07T11:45:32Z"],["dc.date.issued","2014"],["dc.description.abstract","The dopaminergic (DAergic) nigrostriatal tract has an intrinsic regenerative capacity which can be impaired in Parkinson's disease (PD). Alpha-synuclein (aSyn) is a major pathogenic component in PD but its impact on DAergic axonal regeneration is largely unknown. In this study, we expressed pathogenic variants of human aSyn by means of recombinant adeno-associated viral vectors in experimental paradigms of DAergic regeneration. In a scratch lesion model in vitro, both aSyn(A30P) and aSyn(A53T) significantly reduced DAergic neurite regeneration and induced loss of TH-immunopositive cells while aSyn(WT) showed only minor cellular neurotoxic effects. The striatal density of TH-immunopositive axons in the striatal 6-OHDA lesion mouse model was attenuated only by aSyn(A30P). However, striatal expression levels of the regeneration marker GAP-43 in TH-immunopositive fibers were reduced by both aSyn(A30P) and aSyn(A53T), but not by aSyn(WT), which was associated with an activation of the ROCK signaling pathway. Nigral DAergic cell loss was only mildly enhanced by additional overexpression of aSyn variants. Our findings indicate that mutations of aSyn have a strong impact on the regenerative capacity of DAergic neurons, which may contribute to their pathogenic effects."],["dc.description.sponsorship","Open-Access Publikationsfonds 2014"],["dc.format.extent","10"],["dc.identifier.doi","10.3389/fnagi.2014.00239"],["dc.identifier.gro","3142053"],["dc.identifier.isi","000341696200001"],["dc.identifier.pmid","25309425"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10893"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4023"],["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","1663-4365"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Alpha-synuclein mutations impair axonal regeneration in models 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.artnumber","e2000374"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","de Oliveira, Rita Machado"],["dc.contributor.author","Miranda, Hugo Vicente"],["dc.contributor.author","Francelle, Laetitia"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Szegoe, Eva Monika"],["dc.contributor.author","Martinho, Renato"],["dc.contributor.author","Munari, Francesca"],["dc.contributor.author","Lazaro, Diana F."],["dc.contributor.author","Moniot, Sebastien"],["dc.contributor.author","Guerreiro, Patricia S."],["dc.contributor.author","Fonseca, Luis"],["dc.contributor.author","Marijanovic, Zrinka"],["dc.contributor.author","Antas, Pedro"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Enguita, Francisco Javier"],["dc.contributor.author","Fauvet, Bruno"],["dc.contributor.author","Penque, Deborah"],["dc.contributor.author","Pais, Teresa Faria"],["dc.contributor.author","Tong, Qiang"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Kuegler, Sebastian"],["dc.contributor.author","Lashuel, Hilal Ahmed"],["dc.contributor.author","Steegborn, Clemens"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T10:26:48Z"],["dc.date.available","2018-11-07T10:26:48Z"],["dc.date.issued","2017"],["dc.description.abstract","Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. Sirtuin 2 was previously shown to modulate proteotoxicity associated with ageassociated neurodegenerative disorders such as Alzheimer and Parkinson disease (PD). However, the precise molecular mechanisms involved remain unclear. Here, we provide mechanistic insight into the interplay between sirtuin 2 and alpha-synuclein, the major component of the pathognomonic protein inclusions in PD and other synucleinopathies. We found that alpha-synuclein is acetylated on lysines 6 and 10 and that these residues are deacetylated by sirtuin 2. Genetic manipulation of sirtuin 2 levels in vitro and in vivo modulates the levels of alpha-synuclein acetylation, its aggregation, and autophagy. Strikingly, mutants blocking acetylation exacerbate alpha-synuclein toxicity in vivo, in the substantia nigra of rats. Our study identifies alpha-synuclein acetylation as a key regulatory mechanism governing alpha-synuclein aggregation and toxicity, demonstrating the potential therapeutic value of sirtuin 2 inhibition in synucleinopathies."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1371/journal.pbio.2000374"],["dc.identifier.isi","000397909600002"],["dc.identifier.pmid","28257421"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14377"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43121"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Public Library Science"],["dc.relation.haserratum","/handle/2/102935"],["dc.relation.issn","1545-7885"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease"],["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","61"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","77"],["dc.bibliographiccitation.volume","56"],["dc.contributor.author","Repici, Mariaelena"],["dc.contributor.author","Hassanjani, Mahdieh"],["dc.contributor.author","Maddison, Daniel C."],["dc.contributor.author","Garção, Pedro"],["dc.contributor.author","Cimini, Sara"],["dc.contributor.author","Patel, Bhavini"],["dc.contributor.author","Szegö, Éva M."],["dc.contributor.author","Straatman, Kornelis R."],["dc.contributor.author","Lilley, Kathryn S."],["dc.contributor.author","Borsello, Tiziana"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Panman, Lia"],["dc.contributor.author","Giorgini, Flaviano"],["dc.date.accessioned","2020-12-10T14:14:28Z"],["dc.date.available","2020-12-10T14:14:28Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1007/s12035-018-1084-y"],["dc.identifier.eissn","1559-1182"],["dc.identifier.issn","0893-7648"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15569"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71349"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The Parkinson’s Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3471"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Endocrinology"],["dc.bibliographiccitation.lastpage","3482"],["dc.bibliographiccitation.volume","152"],["dc.contributor.author","Koeszegi, Zsombor"],["dc.contributor.author","Szegoe, Eva Monika"],["dc.contributor.author","Cheong, Rachel Y."],["dc.contributor.author","Tolod-Kemp, Emeline"],["dc.contributor.author","Abraham, Istvan M."],["dc.date.accessioned","2018-11-07T08:52:47Z"],["dc.date.available","2018-11-07T08:52:47Z"],["dc.date.issued","2011"],["dc.description.abstract","17 beta-Estradiol (E2) treatment exerts rapid, nonclassical actions via intracellular signal transduction system in basal forebrain cholinergic (BFC) neurons in vivo. Here we examined the effect of E2 treatment on lesioned BFC neurons in ovariectomized mice and the role of E2-induced nonclassical action in this treatment. Mice given an N-methyl-D-aspartic acid (NMDA) injection into the substantia innominata-nucleus basalis magnocellularis complex (SI-NBM) exhibited cholinergic cell loss in the SI-NBM and ipsilateral cholinergic fiber loss in the cortex. A single injection of E2 after NMDA lesion did not have an effect on cholinergic cell loss in the SI-NBM, but it restored the ipsilateral cholinergic fiber density in the cortex in a time- and dose-dependent manner. The most effective cholinergic fiber restoration was observed with 33 ng/g E2 treatment at 1 h after NMDA lesion. The E2-induced cholinergic fiber restoration was absent in neuron-specific estrogen receptor-alpha knockout mice in vivo. Selective activation of nonclassical estrogen signaling in vivo by estren induced E2-like restorative actions. Selective blockade of the MAPK or protein kinase A pathway in vivo prevented E2's ability to restore cholinergic fiber loss. Finally, studies in intact female mice revealed an E2-induced restorative effect that was similar to that of E2-treated ovariectomized mice. These observations demonstrate that a single E2 treatment restores the BFC fiber loss in the cortex, regardless of endogenous E2 levels. They also reveal the critical role of nonclassical estrogen signaling via estrogen receptor-alpha and protein kinase A-MAPK pathways in E2-induced restorative action in the cholinergic system in vivo. (Endocrinology 152: 3471-3482, 2011)"],["dc.identifier.doi","10.1210/en.2011-1017"],["dc.identifier.isi","000294161000019"],["dc.identifier.pmid","21791565"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8027"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22255"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Endocrine Soc"],["dc.relation.issn","0013-7227"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Postlesion Estradiol Treatment Increases Cortical Cholinergic Innervations via Estrogen Receptor-alpha Dependent Nonclassical Estrogen Signaling in Vivo"],["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","90"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neuroendocrinology"],["dc.bibliographiccitation.lastpage","105"],["dc.bibliographiccitation.volume","93"],["dc.contributor.author","Szegő, Éva Mónica"],["dc.contributor.author","Csorba, Attila"],["dc.contributor.author","Janáky, Tamás"],["dc.contributor.author","Kékesi, Katalin A."],["dc.contributor.author","Ábrahám, István M."],["dc.contributor.author","Mórotz, Gábor M."],["dc.contributor.author","Penke, Botond"],["dc.contributor.author","Palkovits, Miklós"],["dc.contributor.author","Murvai, Ünige"],["dc.contributor.author","Kellermayer, Miklós S. Z."],["dc.contributor.author","Kardos, József"],["dc.contributor.author","Juhász, Gábor D."],["dc.date.accessioned","2018-11-07T09:01:47Z"],["dc.date.available","2018-11-07T09:01:47Z"],["dc.date.issued","2011"],["dc.description.abstract","Alzheimer disease is characterized by accumulation of P-amyloid (A beta) and cognitive dysfunctions linked to early loss of cholinergic neurons. As estrogen-based hormone replacement therapy has beneficial effects on cognition of demented patients, and it may prevent memory impairments, we investigated the effect of estrogen-pretreatment on A beta-induced cholinergic neurodegeneration in the nucleus basalis magnocellularis (NBM). We tested which A beta species induces the more pronounced cholinotoxic effect in vivo. We injected different A beta assemblies in the NBM of mice, and measured cholinergic cell and cortical fiber loss. Spherical A beta oligomers had the most toxic effect. Pretreatment of ovariectomized mice with estrogen before A beta injection decreased cholinergic neuron loss and partly prevented fiber degeneration. By using proteomics, we searched for proteins involved in estrogen-mediated protection and in A beta toxicity 24 h following injection. The change in expression of, e.g., DJ-1, NADH ubiquinone oxidoreductase, ATP synthase, phosphatidylethanolamine-binding protein 1, protein phosphatase 2A and dimethylarginine dimethylaminohydrolase 1 support our hypothesis that A beta induces mitochondrial dysfunction, decreases MAPK signaling, and increases NOS activation in NBM. On the other hand, altered expression of, e.g., MAP kinase kinase 1 and 2, protein phosphatase 1 and 2A by A beta might increase MAPK suppression and NOS signaling in the cortical target area. Estrogen pretreatment reversed most of the changes in the proteome in both areas. Our experiments suggest that regulation of the MAPK pathway, mitochondrial pH and NO production may all contribute to A beta toxicity, and their regulation can be prevented partly by estrogen pretreatment. Copyright (C) 2010 S. Karger AG, Basel"],["dc.identifier.doi","10.1159/000321119"],["dc.identifier.isi","000288574900003"],["dc.identifier.pmid","20938166"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8036"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24518"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","S. Karger AG"],["dc.relation.eissn","1423-0194"],["dc.relation.issn","0028-3835"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Effects of Estrogen on Beta-Amyloid-Induced Cholinergic Cell Death in the Nucleus Basalis Magnocellularis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]