Rezaei-Ghaleh, Nasrollah

[["dc.bibliographiccitation.firstpage","4913"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Journal of the American Chemical Society"],["dc.bibliographiccitation.lastpage","4919"],["dc.bibliographiccitation.volume","136"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Amininasab, Mehriar"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Kumar, Sathish"],["dc.contributor.author","Stuendl, Anne"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Walter, Jochen"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2018-11-07T09:41:25Z"],["dc.date.available","2018-11-07T09:41:25Z"],["dc.date.issued","2014"],["dc.description.abstract","Pathogenesis of Alzheimer's disease (AD) is associated with aggregation of the amyloid-beta (A beta) peptide into oligomeric and fibrillar assemblies; however, little is known about the molecular basis of aggregation of A beta into distinct assembly states. Here we demonstrate that phosphorylation at serine 26 (S26) impairs A beta fibrillization while stabilizing its monomers and nontoxic soluble assemblies of nonfibrillar morphology. NMR spectroscopy and replica-exchange molecular dynamics indicate that introduction of a phosphate group or phosphomimetic at position 26 diminishes A beta's propensity to form a beta-hairpin, rigidifies the region around the modification site, and interferes with formation of a fibril-specific salt bridge between aspartic acid 23 and lysine 28. The combined data demonstrate that phosphorylation of S26 prevents a distinct conformational rearrangement that is required for progression of A beta aggregation toward fibrils and provide a basis for a possible role of phosphorylation at serine 26 in AD."],["dc.description.sponsorship","DFG [ZW 71/2-2, ZW 71/3-2, WA1477/6-2]"],["dc.identifier.doi","10.1021/ja411707y"],["dc.identifier.isi","000333947900030"],["dc.identifier.pmid","24617810"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33723"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Chemical Soc"],["dc.relation.issn","0002-7863"],["dc.title","Turn Plasticity Distinguishes Different Modes of Amyloid-beta Aggregation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","16059"],["dc.bibliographiccitation.issue","31"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","16067"],["dc.bibliographiccitation.volume","291"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Kumar, Sathish"],["dc.contributor.author","Walter, Jochen"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2020-12-10T18:12:56Z"],["dc.date.available","2020-12-10T18:12:56Z"],["dc.date.issued","2016"],["dc.description.abstract","Neurodegeneration is characterized by the ubiquitous presence of modifications in protein deposits. Despite their potential significance in the initiation and progression of neurodegenerative diseases, the effects of posttranslational modifications on the molecular properties of protein aggregates are largely unknown. Here, we study the Alzheimer disease-related amyloid-beta (A beta) peptide and investigate how phosphorylation at serine 8 affects the structure of A beta aggregates. Serine 8 is shown to be located in a region of high conformational flexibility in monomeric A beta, which upon phosphorylation undergoes changes in local conformational dynamics. Using hydrogen-deuterium exchange NMR and fluorescence quenching techniques, we demonstrate that A beta phosphorylation at serine 8 causes structural changes in the N-terminal region of A beta aggregates in favor of less compact conformations. Structural changes induced by serine 8 phosphorylation can provide a mechanistic link between phosphorylation and other biological events that involve the N-terminal region of A beta aggregates. Our data therefore support an important role of posttranslational modifications in the structural polymorphism of amyloid aggregates and their modulatory effect on neurodegeneration."],["dc.identifier.doi","10.1074/jbc.M116.728956"],["dc.identifier.eissn","1083-351X"],["dc.identifier.isi","000380585400012"],["dc.identifier.issn","0021-9258"],["dc.identifier.pmid","27252381"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/74537"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.title","Phosphorylation Interferes with Maturation of Amyloid-β Fibrillar Structure in the N Terminus"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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"]]