Savastano, Adriana

[["dc.bibliographiccitation.firstpage","101"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Alzheimer s Disease"],["dc.bibliographiccitation.lastpage","110"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Savastano, Adriana"],["dc.contributor.author","Klafki, Hans"],["dc.contributor.author","Haussman, Ute"],["dc.contributor.author","Oberstein, Timo Jan"],["dc.contributor.author","Mueller, Petr"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2018-11-07T10:21:48Z"],["dc.date.available","2018-11-07T10:21:48Z"],["dc.date.issued","2016"],["dc.description.abstract","According to the modified amyloid hypothesis, the key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of neurotoxic amyloid beta-peptides (A beta s) in plaques and cerebral blood vessels. Additionally to full-length peptides, a great diversity of N-truncated A beta variants is derived from the larger amyloid-beta protein precursor (A beta PP). Vast evidence suggests that A beta(x-42) isoforms play an important role in triggering neurodegeneration due to their high abundance, amyloidogenic propensity and toxicity. Although N-truncated Ap peptides and A beta(x-42) species appear to be the crucial players in AD etiology, the A beta(2-x) isoforms did not receive much attention yet. The present study is the first to show immunohistochemical evidence of A beta(2-x) in cases of AD and its distribution in Al3PP/PS 1KI and 5XFAD transgenic mouse models using a novel antibody pAB77 that has been developed using A132-14 as antigen. Positive plaques and congophilic amyloid angiopathy (CAA) were observed in AD cases and in both mouse models. While in AD cases, abundant CAA and less pronounced plaque pathology was evident, the two mouse models showed predominantly extracellular Ap deposits and minor CAA staining. Western blotting and a capillary isoelectric focusing immunoassay demonstrated the high specificity of the antibody pAb77 against A13-variants starting with the N-terminal Alanine-2."],["dc.identifier.doi","10.3233/JAD-150394"],["dc.identifier.isi","000364409100012"],["dc.identifier.pmid","26529393"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42160"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Ios Press"],["dc.relation.issn","1875-8908"],["dc.relation.issn","1387-2877"],["dc.title","N-Truncated A beta(2-X) Starting with Position Two in Sporadic Alzheimer's Disease Cases and Two Alzheimer Mouse Models"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.volume","119"],["dc.contributor.author","Cario, Alisa"],["dc.contributor.author","Savastano, Adriana"],["dc.contributor.author","Wood, Neil B."],["dc.contributor.author","Liu, Zhu"],["dc.contributor.author","Previs, Michael J."],["dc.contributor.author","Hendricks, Adam G."],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Berger, Christopher L."],["dc.date.accessioned","2022-04-01T10:02:46Z"],["dc.date.available","2022-04-01T10:02:46Z"],["dc.date.issued","2022"],["dc.description.abstract","Significance The microtubule-associated protein Tau is strongly linked to a number of neurological diseases. Disease onset is typically associated with weakened interaction with the microtubule, but this widely accepted model is based on hyperphosphorylation or mutations within the C-terminal microtubule-binding domain of Tau. Here, we find that an N-terminal disease-associated mutation in Tau, R5L, does not reduce Tau affinity for microtubules but instead, modifies the N-terminal structure, altering Tau’s behavior and ability to condense on the microtubule surface. Our findings challenge the current paradigms of both how mutations in Tau lead to disease and the functional role of the N-terminal region of Tau."],["dc.identifier.doi","10.1073/pnas.2114215119"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/106002"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0/"],["dc.title","The pathogenic R5L mutation disrupts formation of Tau complexes on the microtubule by altering local N-terminal structure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Protein Science"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Zachrdla, Milan"],["dc.contributor.author","Savastano, Adriana"],["dc.contributor.author","Ibáñez de Opakua, Alain"],["dc.contributor.author","Cima‐Omori, Maria‐Sol"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2022-09-01T09:50:32Z"],["dc.date.available","2022-09-01T09:50:32Z"],["dc.date.issued","2022"],["dc.description.sponsorship"," H2020 European Research Council https://doi.org/10.13039/100010663"],["dc.identifier.doi","10.1002/pro.4409"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113734"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","1469-896X"],["dc.relation.issn","0961-8368"],["dc.rights.uri","http://creativecommons.org/licenses/by-nc-nd/4.0/"],["dc.title","Contributions of the N‐terminal intrinsically disordered region of the severe acute respiratory syndrome coronavirus 2 nucleocapsid protein to RNA‐induced phase separation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","101"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Alzheimer's Disease"],["dc.bibliographiccitation.lastpage","110"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Savastano, Adriana"],["dc.contributor.author","Klafki, Hans"],["dc.contributor.author","Haußmann, Ute"],["dc.contributor.author","Oberstein, Timo Jan"],["dc.contributor.author","Muller, Petr"],["dc.contributor.author","Wirths, Oliver"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Bayer, Thomas A."],["dc.date.accessioned","2017-09-07T11:44:34Z"],["dc.date.available","2017-09-07T11:44:34Z"],["dc.date.issued","2015"],["dc.description.abstract","According to the modified amyloid hypothesis, the key event in the pathogenesis of Alzheimer’s disease (AD) is the deposition of neurotoxic amyloid β-peptides (Aβs) in plaques and cerebral blood vessels. Additionally to full-length peptides, a great diversity of N-truncated Aβ variants is derived from the larger amyloid-β protein precursor (AβPP). Vast evidence suggests that Aβx-42 isoforms play an important role in triggering neurodegeneration due to their high abundance, amyloidogenic propensity and toxicity. Although N-truncated Aβ peptides and Aβx-42 species appear to be the crucial players in AD etiology, the Aβ2-X isoforms did not receive much attention yet. The present study is the first to show immunohistochemical evidence of Aβ2-X in cases of AD and its distribution in AβPP/PS1KI and 5XFAD transgenic mouse models using a novel antibody pAB77 that has been developed using Aβ2-14 as antigen. Positive plaques and congophilic amyloid angiopathy (CAA) were observed in AD cases and in both mouse models. While in AD cases, abundant CAA and less pronounced plaque pathology was evident, the two mouse models showed predominantly extracellular Aβ deposits and minor CAA staining. Western blotting and a capillary isoelectric focusing immunoassay demonstrated the high specificity of the antibody pAb77 against Aβ-variants starting with the N-terminal Alanine-2."],["dc.identifier.doi","10.3233/jad-150394"],["dc.identifier.gro","3151701"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8520"],["dc.language.iso","en"],["dc.notes.status","public"],["dc.notes.submitter","chake"],["dc.relation.issn","1387-2877"],["dc.title","N-Truncated Aβ2-X Starting with Position Two in Sporadic Alzheimer’s Disease Cases and Two Alzheimer Mouse Models"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Nature Chemistry"],["dc.contributor.author","Ibáñez de Opakua, Alain"],["dc.contributor.author","Geraets, James A."],["dc.contributor.author","Frieg, Benedikt"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Savastano, Adriana"],["dc.contributor.author","Rankovic, Marija"],["dc.contributor.author","Cima-Omori, Maria-Sol"],["dc.contributor.author","Schröder, Gunnar F."],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2022-10-04T10:21:34Z"],["dc.date.available","2022-10-04T10:21:34Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n Proteins that contain repeat phenylalanine-glycine (FG) residues phase separate into oncogenic transcription factor condensates in malignant leukaemias, form the permeability barrier of the nuclear pore complex and mislocalize in neurodegenerative diseases. Insights into the molecular interactions of FG-repeat nucleoporins have, however, remained largely elusive. Using a combination of NMR spectroscopy and cryoelectron microscopy, we have identified uniformly spaced segments of transient β-structure and a stable preformed α-helix recognized by messenger RNA export factors in the FG-repeat domain of human nucleoporin 98 (Nup98). In addition, we have determined at high resolution the molecular organization of reversible FG–FG interactions in amyloid fibrils formed by a highly aggregation-prone segment in Nup98. We have further demonstrated that amyloid-like aggregates of the FG-repeat domain of Nup98 have low stability and are reversible. Our results provide critical insights into the molecular interactions underlying the self-association and phase separation of FG-repeat nucleoporins in physiological and pathological cell activities."],["dc.identifier.doi","10.1038/s41557-022-01035-7"],["dc.identifier.pii","1035"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114448"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-600"],["dc.relation.eissn","1755-4349"],["dc.relation.issn","1755-4330"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Molecular interactions of FG nucleoporin repeats at high resolution"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]