Outeiro, Tiago Fleming

[["dc.bibliographiccitation.firstpage","511"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","526"],["dc.bibliographiccitation.volume","141"],["dc.contributor.author","Erskine, Daniel"],["dc.contributor.author","Koss, David"],["dc.contributor.author","Korolchuk, Viktor I."],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Attems, Johannes"],["dc.contributor.author","McKeith, Ian"],["dc.date.accessioned","2021-04-14T08:30:40Z"],["dc.date.available","2021-04-14T08:30:40Z"],["dc.date.issued","2021"],["dc.description.abstract","Accumulation of the protein α-synuclein into insoluble intracellular deposits termed Lewy bodies (LBs) is the characteristic neuropathological feature of LB diseases, such as Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with LB (DLB). α-Synuclein aggregation is thought to be a critical pathogenic event in the aetiology of LB disease, based on genetic analyses, fundamental studies using model systems, and the observation of LB pathology in post-mortem tissue. However, some monogenic disorders not traditionally characterised as synucleinopathies, such as lysosomal storage disorders, iron storage disorders and mitochondrial diseases, appear disproportionately vulnerable to the deposition of LBs, perhaps suggesting the process of LB formation may be a result of processes perturbed as a result of these conditions. The present review discusses biological pathways common to monogenic disorders associated with LB formation, identifying catabolic processes, particularly related to lipid homeostasis, autophagy and mitochondrial function, as processes that could contribute to LB formation. These findings are discussed in the context of known mediators of α-synuclein aggregation, highlighting the potential influence of impairments to these processes in the aetiology of LB formation."],["dc.identifier.doi","10.1007/s00401-021-02266-7"],["dc.identifier.pmid","33515275"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83330"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/215"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/96"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | B06: Die Rolle von RNA in Synapsenphysiologie und Neurodegeneration"],["dc.relation","SFB 1286 | B08: Definition von Kaskaden molekularer Veränderungen bei Synucleinopathien während der Neurodegeneration"],["dc.relation.eissn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.rights","CC BY 4.0"],["dc.title","Lipids, lysosomes and mitochondria: insights into Lewy body formation from rare monogenic disorders"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","overview_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Brain: A Journal of Neurology"],["dc.contributor.author","Hatton, Christopher"],["dc.contributor.author","Ghanem, Simona S."],["dc.contributor.author","Koss, David J."],["dc.contributor.author","Abdi, Ilham Y."],["dc.contributor.author","Gibbons, Elizabeth"],["dc.contributor.author","Guerreiro, Rita"],["dc.contributor.author","Bras, Jose"],["dc.contributor.author","Walker, Lauren"],["dc.contributor.author","Gelpi, Ellen"],["dc.contributor.author","Heywood, Wendy"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Attems, Johannes"],["dc.contributor.author","McFarland, Robert"],["dc.contributor.author","Forsyth, Rob"],["dc.contributor.author","El-Agnaf, Omar M."],["dc.contributor.author","Erskine, Daniel"],["dc.date.accessioned","2022-02-22T15:58:07Z"],["dc.date.available","2022-02-22T15:58:07Z"],["dc.date.issued","2022-01-06"],["dc.description.abstract","Krabbe disease is an infantile neurodegenerative disorder resulting from pathogenic variants in the GALC gene which causes accumulation of the toxic sphingolipid psychosine. GALC variants are also associated with Lewy body diseases, an umbrella term for age-associated neurodegenerative diseases in which the protein α-synuclein aggregates into Lewy bodies. To explore whether α-synuclein in Krabbe disease has pathological similarities to that in Lewy body disease, we performed an observational post-mortem study of Krabbe disease brain tissue (N = 4) compared to infant controls (N = 4) and identified widespread accumulations of α-synuclein. To determine whether α-synuclein in Krabbe disease brain displayed disease-associated pathogenic properties we evaluated its seeding capacity using the real-time quaking-induced conversion assay in two cases for which frozen tissue was available and strikingly identified aggregation into fibrils similar to those observed in Lewy body disease, confirming the prion-like capacity of Krabbe disease-derived α-synuclein. These observations constitute the first report of prion-like α-synuclein in the brain tissue of infants and challenge the putative view that α-synuclein pathology is merely an age-associated phenomenon, instead suggesting it results from alterations to biological pathways, such as sphingolipid metabolism. Our findings have important implications for understanding the mechanisms underlying Lewy body formation in Lewy body disease."],["dc.identifier.doi","10.1093/brain/awac002"],["dc.identifier.pmid","34999780"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100198"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/388"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/148"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation.eissn","1460-2156"],["dc.relation.issn","0006-8950"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.rights","CC BY-NC 4.0"],["dc.title","Prion-like α-synuclein pathology in the brain of infants with Krabbe disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","unpublished"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","5"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurodegeneration"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Koss, David J."],["dc.contributor.author","Erskine, Daniel"],["dc.contributor.author","Walker, Lauren"],["dc.contributor.author","Kurzawa-Akanbi, Marzena"],["dc.contributor.author","Burn, David"],["dc.contributor.author","Donaghy, Paul"],["dc.contributor.author","Morris, Christopher"],["dc.contributor.author","Taylor, John-Paul"],["dc.contributor.author","Thomas, Alan"],["dc.contributor.author","Attems, Johannes"],["dc.contributor.author","McKeith, Ian"],["dc.date.accessioned","2019-07-09T11:51:10Z"],["dc.date.available","2019-07-09T11:51:10Z"],["dc.date.issued","2019"],["dc.description.abstract","Dementia with Lewy bodies (DLB) is an age-associated neurodegenerative disorder producing progressive cognitive decline that interferes with normal life and daily activities. Neuropathologically, DLB is characterised by the accumulation of aggregated α-synuclein protein in Lewy bodies and Lewy neurites, similar to Parkinson's disease (PD). Extrapyramidal motor features characteristic of PD, are common in DLB patients, but are not essential for the clinical diagnosis of DLB. Since many PD patients develop dementia as disease progresses, there has been controversy about the separation of DLB from PD dementia (PDD) and consensus reports have put forward guidelines to assist clinicians in the identification and management of both syndromes. Here, we present basic concepts and definitions, based on our current understanding, that should guide the community to address open questions that will, hopefully, lead us towards improved diagnosis and novel therapeutic strategies for DLB and other synucleinopathies."],["dc.identifier.doi","10.1186/s13024-019-0306-8"],["dc.identifier.pmid","30665447"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16061"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59887"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","006"],["dc.subject.ddc","573"],["dc.subject.ddc","612"],["dc.title","Dementia with Lewy bodies: an update and outlook"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]