Zafar, Saima

[["dc.bibliographiccitation.firstpage","14166"],["dc.bibliographiccitation.issue","22"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Noor, Aneeqa"],["dc.contributor.author","Younas, Neelam"],["dc.contributor.author","Shafiq, Mohsin"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Wurster, Isabel"],["dc.contributor.author","Brockmann, Kathrin"],["dc.contributor.author","Gasser, Thomas"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2022-12-01T08:31:42Z"],["dc.date.available","2022-12-01T08:31:42Z"],["dc.date.issued","2022"],["dc.description.abstract","β-glucocerebrosidase (GBA)-associated mutations are a significant risk factor for Parkinson’s disease (PD) that aggravate the disease pathology by upregulating the deposition of α-Synuclein (α-Syn). The resultant clinical profile varies for PD patients without GBA mutations. The current study aimed to identify the proteomic targets involved in the pathogenic pathways leading to the differential clinical presentation of GBA-associated PD. CSF samples (n = 32) were obtained from PD patients with GBA mutations (n = 22), PD patients without GBA mutations (n = 7), and healthy controls that were carriers of GBA mutations (n = 3). All samples were subjected to in-gel tryptic digestion followed by the construction of the spectral library and quantitative SWATH-based analysis. CSF α-Syn levels were reduced in both PDIdiopathic and PDGBA cases. Our SWATH-based mass spectrometric analysis detected 363 proteins involved in immune response, stress response, and cell signaling in various groups. Intergroup analysis showed that 52 proteins were significantly up- or downregulated in various groups. Of these 52 targets, 20 proteins were significantly altered in PDGBA cases only while 2 showed different levels in PDIdiopathic patients. Our results show that the levels of several pathologically relevant proteins, including Contactin-1, Selenium-binding protein 1, Adhesion G Protein-Coupled Receptor, and Apolipoprotein E are significantly different among the sporadic and genetic variants of PD and hint at aggravated synaptic damage, oxidative stress, neuronal loss, and aggregation of α-Syn in PDGBA cases."],["dc.identifier.doi","10.3390/ijms232214166"],["dc.identifier.pii","ijms232214166"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/118243"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.eissn","1422-0067"],["dc.title","SWATH Mass Spectrometry-Based CSF Proteome Profile of GBA-Linked Parkinson’s Disease Patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.contributor.author","Noor, Aneeqa"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Shafiq, Mohsin"],["dc.contributor.author","Younas, Neelam"],["dc.contributor.author","Siegert, Anna"],["dc.contributor.author","Mann, Florian A."],["dc.contributor.author","Kruss, Sebastian"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Dihazi, Hassan"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2021-12-01T09:23:29Z"],["dc.date.available","2021-12-01T09:23:29Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract The molecular determinants of atypical clinical variants of Alzheimer’s disease, including the recently discovered rapidly progressive Alzheimer’s disease (rpAD), are unknown to date. Fibrilization of the amyloid-β (Aβ) peptide is the most frequently studied candidate in this context. The Aβ peptide can exist as multiple proteoforms that vary in their post-translational processing, amyloidogenesis, and toxicity. The current study was designed to identify these variations in Alzheimer’s disease patients exhibiting classical (sAD) and rapid progression, with the primary aim of establishing if these variants may constitute strains that underlie the phenotypic variability of Alzheimer’s disease. We employed two-dimensional polyacrylamide gel electrophoresis and MALDI-ToF mass spectrometry to validate and identify the Aβ proteoforms extracted from targeted brain tissues. The biophysical analysis was conducted using RT-QuIC assay, confocal microscopy, and atomic force microscopy. Interactome analysis was performed by co-immunoprecipitation. We present a signature of 33 distinct pathophysiological proteoforms, including the commonly targeted Aβ 40 , Aβ 42 , Aβ 4-42 , Aβ 11-42 , and provide insight into their synthesis and quantities. Furthermore, we have validated the presence of highly hydrophobic Aβ seeds in rpAD brains that seeded reactions at a slower pace in comparison to typical Alzheimer’s disease. In vitro and in vivo analyses also verified variations in the molecular pathways modulated by brain-derived Aβ. These variations in the presence, synthesis, folding, and interactions of Aβ among sAD and rpAD brains constitute important points of intervention. Further validation of reported targets and mechanisms will aid in the diagnosis of and therapy for Alzheimer’s disease."],["dc.description.abstract","Abstract The molecular determinants of atypical clinical variants of Alzheimer’s disease, including the recently discovered rapidly progressive Alzheimer’s disease (rpAD), are unknown to date. Fibrilization of the amyloid-β (Aβ) peptide is the most frequently studied candidate in this context. The Aβ peptide can exist as multiple proteoforms that vary in their post-translational processing, amyloidogenesis, and toxicity. The current study was designed to identify these variations in Alzheimer’s disease patients exhibiting classical (sAD) and rapid progression, with the primary aim of establishing if these variants may constitute strains that underlie the phenotypic variability of Alzheimer’s disease. We employed two-dimensional polyacrylamide gel electrophoresis and MALDI-ToF mass spectrometry to validate and identify the Aβ proteoforms extracted from targeted brain tissues. The biophysical analysis was conducted using RT-QuIC assay, confocal microscopy, and atomic force microscopy. Interactome analysis was performed by co-immunoprecipitation. We present a signature of 33 distinct pathophysiological proteoforms, including the commonly targeted Aβ 40 , Aβ 42 , Aβ 4-42 , Aβ 11-42 , and provide insight into their synthesis and quantities. Furthermore, we have validated the presence of highly hydrophobic Aβ seeds in rpAD brains that seeded reactions at a slower pace in comparison to typical Alzheimer’s disease. In vitro and in vivo analyses also verified variations in the molecular pathways modulated by brain-derived Aβ. These variations in the presence, synthesis, folding, and interactions of Aβ among sAD and rpAD brains constitute important points of intervention. Further validation of reported targets and mechanisms will aid in the diagnosis of and therapy for Alzheimer’s disease."],["dc.identifier.doi","10.1007/s12035-021-02566-9"],["dc.identifier.pii","2566"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94665"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","1559-1182"],["dc.relation.issn","0893-7648"],["dc.title","Molecular Profiles of Amyloid-β Proteoforms in Typical and Rapidly Progressive Alzheimer’s Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

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[["dc.bibliographiccitation.firstpage","317"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","339"],["dc.bibliographiccitation.volume","140"],["dc.contributor.author","Younas, Neelam"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Shafiq, Mohsin"],["dc.contributor.author","Noor, Aneeqa"],["dc.contributor.author","Siegert, Anna"],["dc.contributor.author","Arora, Amandeep Singh"],["dc.contributor.author","Galkin, Alexey"],["dc.contributor.author","Zafar, Ayesha"],["dc.contributor.author","Schmitz, Mathias"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Andreoletti, Olivier"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2021-04-14T08:26:10Z"],["dc.date.available","2021-04-14T08:26:10Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1007/s00401-020-02178-y"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81854"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.title","SFPQ and Tau: critical factors contributing to rapid progression of Alzheimer’s disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]