Outeiro, Tiago Fleming

[["dc.contributor.author","Koss, David J."],["dc.contributor.author","Erskine, Daniel"],["dc.contributor.author","Porter, Andrew"],["dc.contributor.author","Palmoski, Pawel"],["dc.contributor.author","Leite, Marta"],["dc.contributor.author","Attems, Johannes"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2022-08-24T06:03:57Z"],["dc.date.available","2022-08-24T06:03:57Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1101/2021.10.20.465125"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113158"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/486"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/165"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.title","Nuclear alpha-synuclein is present in the human brain and is modified in dementia with Lewy bodies"],["dc.type","preprint"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1141"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Biomedicines"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Jordan, Kate L."],["dc.contributor.author","Koss, David J."],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Giorgini, Flaviano"],["dc.date.accessioned","2022-06-01T09:39:55Z"],["dc.date.available","2022-06-01T09:39:55Z"],["dc.date.issued","2022"],["dc.description.abstract","Rab GTPases (Rabs) are small proteins that play crucial roles in vesicle transport and membrane trafficking. Owing to their widespread functions in several steps of vesicle trafficking, Rabs have been implicated in the pathogenesis of several disorders, including cancer, diabetes, and multiple neurodegenerative diseases. As treatments for neurodegenerative conditions are currently rather limited, the identification and validation of novel therapeutic targets, such as Rabs, is of great importance. This review summarises proof-of-concept studies, demonstrating that modulation of Rab GTPases in the context of Alzheimer’s disease (AD) can ameliorate disease-related phenotypes, and provides an overview of the current state of the art for the pharmacological targeting of Rabs. Finally, we also discuss the barriers and challenges of therapeutically targeting these small proteins in humans, especially in the context of AD."],["dc.identifier.doi","10.3390/biomedicines10051141"],["dc.identifier.pii","biomedicines10051141"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108596"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-572"],["dc.relation.eissn","2227-9059"],["dc.title","Therapeutic Targeting of Rab GTPases: Relevance for Alzheimer’s Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Koss, David J."],["dc.contributor.author","Erskine, Daniel"],["dc.contributor.author","Porter, Andrew"],["dc.contributor.author","Palmoski, Pawel"],["dc.contributor.author","Menon, Hariharan"],["dc.contributor.author","Todd, Olivia G. J."],["dc.contributor.author","Leite, Marta"],["dc.contributor.author","Attems, Johannes"],["dc.contributor.author","Outeiro, Tiago F."],["dc.date.accessioned","2022-09-01T09:50:57Z"],["dc.date.available","2022-09-01T09:50:57Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n \n Dementia with Lewy bodies (DLB) is pathologically defined by the cytoplasmic accumulation of alpha-synuclein (aSyn) within neurons in the brain. Predominately pre-synaptic, aSyn has been reported in various subcellular compartments in experimental models. Indeed, nuclear alpha-synuclein (aSyn\n Nuc\n ) is evident in many models, the dysregulation of which is associated with altered DNA integrity, transcription and nuclear homeostasis. However, the presence of aSyn\n Nuc\n in human brain cells remains controversial, yet the determination of human brain aSyn\n Nuc\n and its pathological modification is essential for understanding synucleinopathies. Here, using a multi-disciplinary approach employing immunohistochemistry, immunoblot, and mass-spectrometry (MS), we confirm aSyn\n Nuc\n in post-mortem brain tissue obtained from DLB and control cases. Highly dependent on antigen retrieval methods, in optimal conditions, intra-nuclear pan and phospho-S129 positive aSyn puncta were observed in cortical neurons and non-neuronal cells in fixed brain sections and in isolated nuclear preparations in all cases examined. Furthermore, an increase in nuclear phospho-S129 positive aSyn immunoreactivity was apparent in DLB cases compared to controls, in both neuronal and non-neuronal cell types. Our initial histological investigations identified that aSyn\n Nuc\n is affected by epitope unmasking methods but present under optimal conditions, and this presence was confirmed by isolation of nuclei and a combined approach of immunoblotting and mass spectrometry, where aSyn\n Nuc\n was approximately tenfold less abundant in the nucleus than cytoplasm. Notably, direct comparison of DLB cases to aged controls identified increased pS129 and higher molecular weight species in the nuclei of DLB cases, suggesting putative pathogenic modifications to aSyn\n Nuc\n in DLB. In summary, using multiple approaches we provide several lines of evidence supporting the presence of aSyn\n Nuc\n in autoptic human brain tissue and, notably, that it is subject to putative pathogenic modifications in DLB that may contribute to the disease phenotype."],["dc.description.sponsorship","The Lewy Body Society"],["dc.description.sponsorship","ARUK Northern network"],["dc.identifier.doi","10.1186/s40478-022-01403-x"],["dc.identifier.pii","1403"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113844"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","2051-5960"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Nuclear alpha-synuclein is present in the human brain and is modified in dementia with Lewy bodies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","535"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","565"],["dc.bibliographiccitation.volume","150"],["dc.contributor.author","Marvian, Amir Tayaranian"],["dc.contributor.author","Koss, David J."],["dc.contributor.author","Aliakbari, Farhang"],["dc.contributor.author","Morshedi, Dina"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2020-12-10T18:29:01Z"],["dc.date.available","2020-12-10T18:29:01Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1111/jnc.14707"],["dc.identifier.pmid","31004503"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/76494"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/11"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | B08: Definition von Kaskaden molekularer Veränderungen bei Synucleinopathien während der Neurodegeneration"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.title","In vitro models of synucleinopathies: informing on molecular mechanisms and protective strategies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","overview_ja"],["dspace.entity.type","Publication"]]