Szegő, Éva Mónica

[["dc.bibliographiccitation.firstpage","3752"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","The Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","3769"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Gong, Jing"],["dc.contributor.author","Szego, Éva M."],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Benito, Eva"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Outeiro, Tiago"],["dc.contributor.author","Schneider, Anja"],["dc.date.accessioned","2020-12-10T18:42:35Z"],["dc.date.available","2020-12-10T18:42:35Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1523/JNEUROSCI.2070-18.2019"],["dc.identifier.pmid","30796158"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78015"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/13"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | B06: Die Rolle von RNA in Synapsenphysiologie und Neurodegeneration"],["dc.relation.workinggroup","RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases)"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.title","Translocator Protein Ligand Protects against Neurodegeneration in the MPTP Mouse Model of Parkinsonism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1399"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","1419"],["dc.bibliographiccitation.volume","140"],["dc.contributor.author","Miranda, Hugo Vicente"],["dc.contributor.author","Szego, Eva M."],["dc.contributor.author","Oliveira, Luis M. A."],["dc.contributor.author","Breda, Carlo"],["dc.contributor.author","Darendelioglu, Ekrem"],["dc.contributor.author","de Oliveira, Rita Machado"],["dc.contributor.author","Ferreira, Diana G."],["dc.contributor.author","Gomes, Marcos Antonio"],["dc.contributor.author","Rott, Ruth"],["dc.contributor.author","Oliveira, Marcia"],["dc.contributor.author","Munari, Francesca"],["dc.contributor.author","Enguita, Francisco Javier"],["dc.contributor.author","Simoes, Tania"],["dc.contributor.author","Rodrigues, Eva F."],["dc.contributor.author","Heinrich, Michael"],["dc.contributor.author","Martins, Ivo C."],["dc.contributor.author","Zamolo, Irina"],["dc.contributor.author","Riess, Olaf"],["dc.contributor.author","Cordeiro, Carlos"],["dc.contributor.author","Ponces-Freire, Ana"],["dc.contributor.author","Lashuel, Hilal Ahmed"],["dc.contributor.author","Santos, Nuno C."],["dc.contributor.author","Lopes, Luisa Vaqueiro"],["dc.contributor.author","Xiang, Wei"],["dc.contributor.author","Jovin, Thomas M."],["dc.contributor.author","Penque, Deborah"],["dc.contributor.author","Engelender, Simone"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Klucken, Jochen"],["dc.contributor.author","Giorgini, Flaviano"],["dc.contributor.author","Quintas, Alexandre"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T10:24:40Z"],["dc.date.available","2018-11-07T10:24:40Z"],["dc.date.issued","2017"],["dc.description.abstract","alpha-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of alpha-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational modification, enhanced alpha-synuclein toxicity in vitro and in vivo, in Drosophila and in mice. Glycation affected primarily the N-terminal region of alpha-synuclein, reducing membrane binding, impaired the clearance of alpha-synuclein, and promoted the accumulation of toxic oligomers that impaired neuronal synaptic transmission. Strikingly, using glycation inhibitors, we demonstrated that normal clearance of alpha-synuclein was re-established, aggregation was reduced, and motor phenotypes in Drosophila were alleviated. Altogether, our study demonstrates glycation constitutes a novel drug target that can be explored in synucleinopathies as well as in other neurodegenerative conditions."],["dc.identifier.doi","10.1093/brain/awx056"],["dc.identifier.isi","000400069900026"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42703"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.haserratum","/handle/2/103764"],["dc.relation.issn","1460-2156"],["dc.relation.issn","0006-8950"],["dc.title","Glycation potentiates alpha-synuclein-associated neurodegeneration in synucleinopathies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2603"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.lastpage","2616"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Pais, Teresa Faria"],["dc.contributor.author","Szego, Eva M."],["dc.contributor.author","Marques, Oldriska"],["dc.contributor.author","Miller-Fleming, Leonor"],["dc.contributor.author","Antas, Pedro"],["dc.contributor.author","Guerreiro, Patricia S."],["dc.contributor.author","de Oliveira, Rita Machado"],["dc.contributor.author","Kasapoglu, Burcu"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T09:18:44Z"],["dc.date.available","2018-11-07T09:18:44Z"],["dc.date.issued","2013"],["dc.description.abstract","Deleterious sustained inflammation mediated by activated microglia is common to most of neurologic disorders. Here, we identified sirtuin 2 (SIRT2), an abundant deacetylase in the brain, as a major inhibitor of microglia-mediated inflammation and neurotoxicity. SIRT2-deficient mice (SIRT2(-/-)) showed morphological changes in microglia and an increase in pro-inflammatory cytokines upon intracortical injection of lipopolysaccharide (LPS). This response was associated with increased nitrotyrosination and neuronal cell death. Interestingly, manipulation of SIRT2 levels in microglia determined the response to Toll-like receptor (TLR) activation. SIRT2 overexpression inhibited microglia activation in a process dependent on serine 331 (S331) phosphorylation. Conversely, reduction of SIRT2 in microglia dramatically increased the expression of inflammatory markers, the production of free radicals, and neurotoxicity. Consistent with increased NF-kappa B-dependent transcription of inflammatory genes, NF-kappa B was found hyperacetylated in the absence of SIRT2, and became hypoacetylated in the presence of S331A mutant SIRT2. This finding indicates that SIRT2 functions as a 'gatekeeper', preventing excessive microglial activation through NF-kappa B deacetylation. Our data uncover a novel role for SIRT2 opening new perspectives for therapeutic intervention in neuroinflammatory disorders."],["dc.identifier.doi","10.1038/emboj.2013.200"],["dc.identifier.isi","000325276800008"],["dc.identifier.pmid","24013120"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28474"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0261-4189"],["dc.title","The NAD-dependent deacetylase sirtuin 2 is a suppressor of microglial activation and brain inflammation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e58"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","e58"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Miranda, Hugo Vicente"],["dc.contributor.author","Szegő, Éva M."],["dc.contributor.author","Oliveira, Luís M. A."],["dc.contributor.author","Breda, Carlo"],["dc.contributor.author","Darendelioglu, Ekrem"],["dc.contributor.author","de Oliveira, Rita M."],["dc.contributor.author","Ferreira, Diana G."],["dc.contributor.author","Gomes, Marcos A."],["dc.contributor.author","Rott, Ruth"],["dc.contributor.author","Oliveira, Márcia"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2022-03-01T11:46:42Z"],["dc.date.available","2022-03-01T11:46:42Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1093/brain/awab175"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103764"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1460-2156"],["dc.relation.iserratumof","/handle/2/42703"],["dc.relation.issn","0006-8950"],["dc.title","Erratum to: Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","erratum_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","90"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of the Neurological Sciences"],["dc.bibliographiccitation.lastpage","95"],["dc.bibliographiccitation.volume","310"],["dc.contributor.author","Szego, Eva M."],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Kermer, Pawel"],["dc.date.accessioned","2018-11-07T08:49:51Z"],["dc.date.available","2018-11-07T08:49:51Z"],["dc.date.issued","2011"],["dc.description.abstract","Cognitive dysfunction can be common among Parkinson's disease (PD) patients, and multiplication of the gene alpha-synuclein (alpha syn) increases the risk of dementia. Here, we studied the role of dopamine-depletion and increased asyn load and aggregation on cholinergic structures in vivo. Wild-type (WT) and mice with A30P asyn overexpression were treated subacutely with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MFTP), and the number of cholinergic cells in their nucleus basalis magnocellularis-substantia innominata (NBM-SI), their cortical fiber density and their expression of different genes 1 day or 90 days after the last MPTP-injection were measured. Long-term dopamine depletion decreased the expression of choline acetyl transferase (ChAT) in the NBM-SI of WT mice, but no neuron loss was observed. In contrast, cortical cholinergic fiber density was decreased three months after MPTP-injection. Increased brain-derived neurotrophic factor expression could maintain cholinergic functions under these conditions. Expression of A30P alpha syn in six-months-old transgenic mice resulted in decreased tyrosine receptor kinase B expression, and lower cortical cholinergic fiber density. Dopamine-depletion by MPTP induced cholinergic cell loss in the NBM-SI and increased cortical fiber loss. Our findings may explain why cholinergic cells are more vulnerable in PD, leading to an increased probability of dementia. (C) 2011 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jns.2011.06.048"],["dc.identifier.isi","000296927500023"],["dc.identifier.pmid","21774947"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21555"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.eventlocation","Barcelona, SPAIN"],["dc.relation.issn","0022-510X"],["dc.title","Dopamine-depletion and increased alpha-synuclein load induce degeneration of cortical cholinergic fibers in mice"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","589"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.lastpage","601"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Szego, Eva M."],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Kermer, Pawel"],["dc.contributor.author","Schulz, Joerg B."],["dc.date.accessioned","2018-11-07T09:28:56Z"],["dc.date.available","2018-11-07T09:28:56Z"],["dc.date.issued","2013"],["dc.description.abstract","Dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) are characterized by loss of acetylcholine (ACh) from cortical areas. Clinical studies report positive effects of acetylcholine esterase (AChE) inhibitors in PDD and dementia with Lewy bodies. We here report that the number of neurons expressing a cholinergic marker in the medial septum-diagonal band of Broca complex decreases in A30P alpha-synuclein-expressing mice during aging, paralleled by a lower AChE fiber density in the dentate gyrus and in the hippocampal CA1 field. After inducing dopamine depletion by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), no acute but a delayed loss of cholinergic neurons and AChE-positive fibers was observed, which was attenuated by L-3,4-dihydroxyphenylalanine (DOPA) treatment. Expression of nerve growth factor (NGF) and tyrosine receptor kinase A (TrkA) genes was upregulated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride-treated wild type mice, but not in A30P alpha-synuclein expressing animals. In contrast, upregulation of sortilin and p75(NTR) genes was found in the A30P alpha-synuclein-expressing mice. These results suggest that dopamine deficiency may contribute to the impairment of the septohippocampal system in patients with PDD and that L-3,4-dihydroxyphenylalanine may not only result in symptomatic treatment of the akinetic-rigid syndrome but may also alleviate the degeneration of basal forebrain cholinergic system and the cognitive decline. (C) 2013 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.neurobiolaging.2012.04.012"],["dc.identifier.isi","000312263200020"],["dc.identifier.pmid","22579457"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30904"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0197-4580"],["dc.title","Impairment of the septal cholinergic neurons in MPTP-treated A30P alpha-synuclein mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","E6506"],["dc.bibliographiccitation.issue","42"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","E6515"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Villar-Pique, Anna"],["dc.contributor.author","da Fonseca, Tomas Lopes"],["dc.contributor.author","Sant'Anna, Ricardo"],["dc.contributor.author","Szegoe, Eva Monika"],["dc.contributor.author","Fonseca-Ornelas, Luis"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Carija, Anita"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Masaracchia, Caterina"],["dc.contributor.author","Gonzalez, Enrique Abad"],["dc.contributor.author","Rossetti, Giulia"],["dc.contributor.author","Carloni, Paolo"],["dc.contributor.author","Fernandez, Claudio O."],["dc.contributor.author","Foguel, Debora"],["dc.contributor.author","Milosevic, Ira"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Ventura, Salvador"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T10:06:57Z"],["dc.date.available","2018-11-07T10:06:57Z"],["dc.date.issued","2016"],["dc.description.abstract","Synucleinopathies are a group of progressive disorders characterized by the abnormal aggregation and accumulation of alpha-synuclein (aSyn), an abundant neuronal protein that can adopt different conformations and biological properties. Recently, aSyn pathology was shown to spread between neurons in a prion-like manner. Proteins like aSyn that exhibit self-propagating capacity appear to be able to adopt different stable conformational states, known as protein strains, which can be modulated both by environmental and by protein-intrinsic factors. Here, we analyzed these factors and found that the unique combination of the neurodegeneration-related metal copper and the pathological H50Q aSyn mutation induces a significant alteration in the aggregation properties of aSyn. We compared the aggregation of WT and H50Q aSyn with and without copper, and assessed the effects of the resultant protein species when applied to primary neuronal cultures. The presence of copper induces the formation of structurally different and less-damaging aSyn aggregates. Interestingly, these aggregates exhibit a stronger capacity to induce aSyn inclusion formation in recipient cells, which demonstrates that the structural features of aSyn species determine their effect in neuronal cells and supports a lack of correlation between toxicity and inclusion formation. In total, our study provides strong support in favor of the hypothesis that protein aggregation is not a primary cause of cytotoxicity."],["dc.identifier.doi","10.1073/pnas.1606791113"],["dc.identifier.isi","000385610400024"],["dc.identifier.pmid","27708160"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39195"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Environmental and genetic factors support the dissociation between alpha-synuclein aggregation and toxicity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","149"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","161"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Yin, Guowei"],["dc.contributor.author","Da Fonseca, Tomas Lopes"],["dc.contributor.author","Eisbach, Sibylle E."],["dc.contributor.author","Anduaga, Ane Martin"],["dc.contributor.author","Breda, Carlo"],["dc.contributor.author","Orcellet, Maria L."],["dc.contributor.author","Szego, Eva M."],["dc.contributor.author","Guerreiro, Patricia"],["dc.contributor.author","Lazar, Diana F."],["dc.contributor.author","Braus, Gerhard H."],["dc.contributor.author","Fernandez, Claudio O."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Goody, Roger S."],["dc.contributor.author","Itzen, Aymelt"],["dc.contributor.author","Giorgini, Flaviano"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:45:30Z"],["dc.date.available","2017-09-07T11:45:30Z"],["dc.date.issued","2014"],["dc.description.abstract","Alpha-synuclein (alpha S) misfolding is associated with Parkinson's disease (PD) but little is known about the mechanisms underlying alpha S toxicity. Increasing evidence suggests that defects in membrane transport play an important role in neuronal dysfunction. Here we demonstrate that the GTPase Rab8a interacts with alpha S in rodent brain. NMR spectroscopy reveals that the C-terminus of alpha S binds to the functionally important switch region as well as the C-terminal tail of Rab8a. In line with a direct Rab8a/alpha S interaction, Rab8a enhanced alpha S aggregation and reduced alpha S-induced cellular toxicity. In addition, Rab8 - the Drosophila ortholog of Rab8a - ameliorated alpha S-oligomer specific locomotor impairment and neuron loss in fruit flies. In support of the pathogenic relevance of the alpha S-Rab8a interaction, phosphorylation of alpha S at S129 enhanced binding to Rab8a, increased formation of insoluble alpha S aggregates and reduced cellular toxicity. Our study provides novel mechanistic insights into the interplay of the GTPase Rab8a and alpha S cytotoxicity, and underscores the therapeutic potential of targeting this interaction. (C) 2014 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.nbd.2014.06.018"],["dc.identifier.gro","3142046"],["dc.identifier.isi","000340691400015"],["dc.identifier.pmid","24983211"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3945"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1095-953X"],["dc.relation.issn","0969-9961"],["dc.title","alpha-Synuclein interacts with the switch region of Rab8a in a Ser129 phosphorylation-dependent manner"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.lastpage","16"],["dc.bibliographiccitation.volume","56"],["dc.contributor.author","Szegő, Éva M."],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2022-03-01T11:45:19Z"],["dc.date.available","2022-03-01T11:45:19Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1016/j.neurobiolaging.2017.04.001"],["dc.identifier.pii","S0197458017301197"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103286"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0197-4580"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","Sirtuin 2 enhances dopaminergic differentiation via the AKT/GSK-3β/β-catenin pathway"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["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"]]