Schmitz, Matthias

[["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"]]

[["dc.bibliographiccitation.artnumber","11"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurodegeneration"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Shafiq, Mohsin"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Younas, Neelam"],["dc.contributor.author","Noor, Aneeqa"],["dc.contributor.author","Puig, Berta"],["dc.contributor.author","Altmeppen, Hermann C."],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Matschke, Jakob"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Glatzel, Markus"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2021-06-01T10:48:05Z"],["dc.date.accessioned","2022-08-16T12:59:31Z"],["dc.date.available","2021-06-01T10:48:05Z"],["dc.date.available","2022-08-16T12:59:31Z"],["dc.date.issued","2021-02-22"],["dc.date.updated","2022-07-29T12:17:40Z"],["dc.description.abstract","Abstract\r\n \r\n Background\r\n High-density oligomers of the prion protein (HDPs) have previously been identified in brain tissues of patients with rapidly progressive Alzheimer’s disease (rpAD). The current investigation aims at identifying interacting partners of HDPs in the rpAD brains to unravel the pathological involvement of HDPs in the rapid progression.\r\n \r\n \r\n Methods\r\n HDPs from the frontal cortex tissues of rpAD brains were isolated using sucrose density gradient centrifugation. Proteins interacting with HDPs were identified by co-immunoprecipitation coupled with mass spectrometry. Further verifications were carried out using proteomic tools, immunoblotting, and confocal laser scanning microscopy.\r\n \r\n \r\n Results\r\n We identified rpAD-specific HDP-interactors, including the growth arrest specific 2-like 2 protein (G2L2). Intriguingly, rpAD-specific disturbances were found in the localization of G2L2 and its associated proteins i.e., the end binding protein 1, α-tubulin, and β-actin.\r\n \r\n \r\n Discussion\r\n The results show the involvement of HDPs in the destabilization of the neuronal actin/tubulin infrastructure. We consider this disturbance to be a contributing factor for the rapid progression in rpAD."],["dc.description.sponsorship","Open-Access-Finanzierung durch die Universitätsmedizin Göttingen 2021"],["dc.identifier.citation","Molecular Neurodegeneration. 2021 Feb 22;16(1):11"],["dc.identifier.doi","10.1186/s13024-021-00422-x"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17736"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85822"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112753"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1750-1326"],["dc.relation.orgunit","Klinik für Neurologie"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Rapidly progressive Alzheimer’s disease"],["dc.subject","rpAD"],["dc.subject","Growth arrest specific proteins"],["dc.subject","GAS"],["dc.subject","Growth arrest specific 2 like 2"],["dc.subject","G2L2"],["dc.subject","Prion protein oligomers"],["dc.subject","PrPC"],["dc.subject","Co-immunoprecipitation"],["dc.subject","Cytoskeleton"],["dc.subject","Actin"],["dc.subject","Tubulin"],["dc.title","Prion protein oligomers cause neuronal cytoskeletal damage in rapidly progressive Alzheimer’s disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurodegeneration"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Shafiq, Mohsin"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Younas, Neelam"],["dc.contributor.author","Noor, Aneeqa"],["dc.contributor.author","Puig, Berta"],["dc.contributor.author","Altmeppen, Hermann Clemens"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Matschke, Jakob"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2021-06-01T10:48:05Z"],["dc.date.available","2021-06-01T10:48:05Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Background High-density oligomers of the prion protein (HDPs) have previously been identified in brain tissues of patients with rapidly progressive Alzheimer’s disease (rpAD). The current investigation aims at identifying interacting partners of HDPs in the rpAD brains to unravel the pathological involvement of HDPs in the rapid progression. Methods HDPs from the frontal cortex tissues of rpAD brains were isolated using sucrose density gradient centrifugation. Proteins interacting with HDPs were identified by co-immunoprecipitation coupled with mass spectrometry. Further verifications were carried out using proteomic tools, immunoblotting, and confocal laser scanning microscopy. Results We identified rpAD-specific HDP-interactors, including the growth arrest specific 2-like 2 protein (G2L2). Intriguingly, rpAD-specific disturbances were found in the localization of G2L2 and its associated proteins i.e., the end binding protein 1, α-tubulin, and β-actin. Discussion The results show the involvement of HDPs in the destabilization of the neuronal actin/tubulin infrastructure. We consider this disturbance to be a contributing factor for the rapid progression in rpAD."],["dc.description.sponsorship","Open-Access-Finanzierung durch die Universitätsmedizin Göttingen 2021"],["dc.identifier.doi","10.1186/s13024-021-00422-x"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17736"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85822"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1750-1326"],["dc.relation.isreplacedby","hdl:null"],["dc.relation.orgunit","Klinik für Neurologie"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Prion protein oligomers cause neuronal cytoskeletal damage in rapidly progressive Alzheimer’s disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]