Kleinknecht, Alexandra

[["dc.bibliographiccitation.firstpage","287"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The Neuroradiology Journal"],["dc.bibliographiccitation.lastpage","293"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Schnieder, M"],["dc.contributor.author","Psychogios, MN"],["dc.contributor.author","Maier, IL"],["dc.contributor.author","Tsogkas, I"],["dc.contributor.author","Schregel, K"],["dc.contributor.author","Kleinknecht, A"],["dc.contributor.author","Knauth, M"],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Liman, Jan"],["dc.contributor.author","Behme, D"],["dc.date.accessioned","2020-12-10T18:38:38Z"],["dc.date.available","2020-12-10T18:38:38Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1177/1971400918791700"],["dc.identifier.eissn","2385-1996"],["dc.identifier.issn","1971-4009"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77395"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","The problem of strict image-based inclusion criteria for mechanical thrombectomy – an analysis of stroke patients with an initial low CBV-ASPECTS score"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","31224"],["dc.bibliographiccitation.issue","45"],["dc.bibliographiccitation.journal","The Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","31240"],["dc.bibliographiccitation.volume","289"],["dc.contributor.author","Shahpasandzadeh, Hedieh"],["dc.contributor.author","Popova, Blagovesta"],["dc.contributor.author","Kleinknecht, Alexandra"],["dc.contributor.author","Fraser, Paul E."],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Braus, Gerhard H."],["dc.date.accessioned","2018-09-28T08:29:52Z"],["dc.date.available","2018-09-28T08:29:52Z"],["dc.date.issued","2014"],["dc.description.abstract","Parkinson disease is associated with the progressive loss of dopaminergic neurons from the substantia nigra. The pathological hallmark of the disease is the accumulation of intracytoplasmic inclusions known as Lewy bodies that consist mainly of post-translationally modified forms of α-synuclein. Whereas phosphorylation is one of the major modifications of α-synuclein in Lewy bodies, sumoylation has recently been described. The interplay between α-synuclein phosphorylation and sumoylation is poorly understood. Here, we examined the interplay between these modifications as well as their impact on cell growth and inclusion formation in yeast. We found that α-synuclein is sumoylated in vivo at the same sites in yeast as in human cells. Impaired sumoylation resulted in reduced yeast growth combined with an increased number of cells with inclusions, suggesting that this modification plays a protective role. In addition, inhibition of sumoylation prevented autophagy-mediated aggregate clearance. A defect in α-synuclein sumoylation could be suppressed by serine 129 phosphorylation by the human G protein-coupled receptor kinase 5 (GRK5) in yeast. Phosphorylation reduced foci formation, alleviated yeast growth inhibition, and partially rescued autophagic α-synuclein degradation along with the promotion of proteasomal degradation, resulting in aggregate clearance in the absence of a small ubiquitin-like modifier. These findings suggest a complex interplay between sumoylation and phosphorylation in α-synuclein aggregate clearance, which may open new horizons for the development of therapeutic strategies for Parkinson disease."],["dc.identifier.doi","10.1074/jbc.M114.559237"],["dc.identifier.pmid","25231978"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15835"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1083-351X"],["dc.title","Interplay between sumoylation and phosphorylation for protection against α-synuclein inclusions"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","617"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biomolecules"],["dc.bibliographiccitation.lastpage","634"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Popova, Blagovesta"],["dc.contributor.author","Kleinknecht, Alexandra"],["dc.contributor.author","Braus, Gerhard H."],["dc.date.accessioned","2018-09-28T07:53:44Z"],["dc.date.available","2018-09-28T07:53:44Z"],["dc.date.issued","2015"],["dc.description.abstract","The budding yeast Saccharomyces cerevisiae represents an established model system to study the molecular mechanisms associated to neurodegenerative disorders. A key-feature of Parkinson's disease is the formation of Lewy bodies, which are cytoplasmic protein inclusions. Misfolded α-synuclein is one of their main constituents. Expression of α-synuclein protein in yeast leads to protein aggregation and cellular toxicity, which is reminiscent to Lewy body containing human cells. The molecular mechanism involved in clearance of α-synuclein aggregates is a central question for elucidating the α-synuclein-related toxicity. Cellular clearance mechanisms include ubiquitin mediated 26S proteasome function as well as lysosome/vacuole associated degradative pathways as autophagy. Various modifications change α-synuclein posttranslationally and alter its inclusion formation, cytotoxicity and the distribution to different clearance pathways. Several of these modification sites are conserved from yeast to human. In this review, we summarize recent findings on the effect of phosphorylation and sumoylation of α-synuclein to the enhanced channeling to either the autophagy or the proteasome degradation pathway in yeast model of Parkinson's disease."],["dc.identifier.doi","10.3390/biom5020617"],["dc.identifier.pmid","25915624"],["dc.identifier.pmid","25915624"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15832"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","2218-273X"],["dc.title","Posttranslational Modifications and Clearing of α-Synuclein Aggregates in Yeast"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]