Rezaei-Ghaleh, Nasrollah

[["dc.bibliographiccitation.artnumber","11359"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Amininasab, Mehriar"],["dc.contributor.author","Kumar, Sathish"],["dc.contributor.author","Walter, Jochen"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2018-11-07T10:16:17Z"],["dc.date.available","2018-11-07T10:16:17Z"],["dc.date.issued","2016"],["dc.description.abstract","Protein aggregation plays a crucial role in neurodegenerative diseases. A key feature of protein aggregates is their ubiquitous modification by phosphorylation. Little is known, however, about the molecular consequences of phosphorylation of protein aggregates. Here we show that phosphorylation of beta-amyloid at serine 8 increases the stability of its pathogenic aggregates against high-pressure and SDS-induced dissociation. We further demonstrate that phosphorylation results in an elevated number of hydrogen bonds at the N terminus of beta-amyloid, the region that is critically regulated by a variety of post-translational modifications. Because of the increased lifetime of phosphorylated beta-amyloid aggregates, phosphorylation can promote the spreading of beta-amyloid in Alzheimer pathogenesis. Our study suggests that regulation of the molecular stability of protein aggregates by post-translational modifications is a crucial factor for disease progression in the brain."],["dc.identifier.doi","10.1038/ncomms11359"],["dc.identifier.isi","000374063100001"],["dc.identifier.pmid","27072999"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13256"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41007"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.title","Phosphorylation modifies the molecular stability of beta-amyloid deposits"],["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","525"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","537"],["dc.bibliographiccitation.volume","131"],["dc.contributor.author","Kumar, Sathish"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Stueber, Kathrin"],["dc.contributor.author","Wunderlich, Patrick"],["dc.contributor.author","Koch, Philipp"],["dc.contributor.author","Theil, Sandra"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Bayer, Thomas A."],["dc.contributor.author","Bruestle, Oliver"],["dc.contributor.author","Thal, Dietmar Rudolf"],["dc.contributor.author","Walter, Jochen"],["dc.date.accessioned","2018-11-07T10:16:30Z"],["dc.date.available","2018-11-07T10:16:30Z"],["dc.date.issued","2016"],["dc.description.abstract","Aggregation and toxicity of the amyloid beta-peptide (A beta) are considered as critical events in the initiation and progression of Alzheimer's disease (AD). Recent evidence indicated that soluble oligomeric A beta assemblies exert pronounced toxicity, rather than larger fibrillar aggregates that deposit in the forms of extracellular plaques. While some rare mutations in the A beta sequence that cause early-onset AD promote the oligomerization, molecular mechanisms that induce the formation or stabilization of oligomers of the wild-type A beta remain unclear. Here, we identified an A beta variant phosphorylated at Ser26 residue (pSer26A beta) in transgenic mouse models of AD and in human brain that shows contrasting spatio-temporal distribution as compared to non-phosphorylated A beta (npA beta) or other modified A beta species. pSer26A beta is particularly abundant in intraneuronal deposits at very early stages of AD, but much less in extracellular plaques. pSer26A beta assembles into a specific oligomeric form that does not proceed further into larger fibrillar aggregates, and accumulates in characteristic intracellular compartments of granulovacuolar degeneration together with TDP-43 and phosphorylated tau. Importantly, pSer26A beta oligomers exert increased toxicity in human neurons as compared to other known A beta species. Thus, pSer26A beta could represent a critical species in the neurodegeneration during AD pathogenesis."],["dc.identifier.doi","10.1007/s00401-016-1546-0"],["dc.identifier.isi","000372297500003"],["dc.identifier.pmid","26898910"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13216"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41051"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","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","Phosphorylation of the amyloid beta-peptide at Ser26 stabilizes oligomeric assembly and increases neurotoxicity"],["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"]]