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Domert, JakobLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Linkoping Univ, Dept Clin Pathol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
(författare)
Aggregated Alpha-Synuclein Transfer Efficiently between Cultured Human Neuron-Like Cells and Localize to Lysosomes
- Artikel/kapitelEngelska2016
Förlag, utgivningsår, omfång ...
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2016-12-28
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Public Library of Science (PLoS),2016
Nummerbeteckningar
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LIBRIS-ID:oai:gup.ub.gu.se/250114
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https://gup.ub.gu.se/publication/250114URI
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https://doi.org/10.1371/journal.pone.0168700DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-134306URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-315074URI
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Funding Agencies|Swedish Research Council [MH: 523-2013-2735]; Swedish Brain Power Program; Research Foundation of the Swedish Parkinsons Disease Association; Ostergotland Research Foundation for Parkinsons Disease; Parkinson Research Foundation; Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research; Gustav V and Queen Victorias Foundation; Swedish Dementia Foundation; Linkoping University Neurobiology Centre; County Council of Ostergotland; Marianne and Marcus Wallenberg Foundation
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Parkinson's disease and other alpha-synucleinopathies are progressive neurodegenerative diseases characterized by aggregates of misfolded alpha-synuclein spreading throughout the brain. Recent evidence suggests that the pathological progression is likely due to neuron-to-neuron transfer of these aggregates between neuroanatomically connected areas of the brain. As the impact of this pathological spreading mechanism is currently debated, we aimed to investigate the transfer and subcellular location of alpha-synuclein species in a novel 3D co-culture human cell model based on highly differentiated SH-SY5Y cells. Fluorescently-labeled monomeric, oligomeric and fibrillar species of alpha-synuclein were introduced into a donor cell population and co-cultured with an EGFP-expressing acceptor-cell population of differentiated neuron-like cells. Subsequent transfer and colocalization of the different species were determined with confocal microscopy. We could confirm cell-to-cell transfer of all three alpha-synuclein species investigated. Interestingly the level of transferred oligomers and fibrils and oligomers were significantly higher than monomers, which could affect the probability of seeding and pathology in the recipient cells. Most alpha-synuclein colocalized with the lysosomal/endosomal system, both pre- and postsynaptically, suggesting its importance in the processing and spreading of alpha-synuclein.
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Sackmann, ChristopherLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Linkoping Univ, Dept Clin Pathol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.(Swepub:liu)chrsa69
(författare)
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Severinsson, EmelieLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Linkoping Univ, Dept Clin Pathol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.(Swepub:liu)emedj24
(författare)
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Agholme, LottaLinköpings universitet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Avdelningen för cellbiologi,Medicinska fakulteten,University of Gothenburg, Sweden,Linkoping Univ, Dept Clin Pathol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden.(Swepub:liu)lothe38
(författare)
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Bergström, JoakimUppsala universitet,Geriatrik(Swepub:uu)joakberg
(författare)
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Ingelsson, MartinUppsala universitet,Geriatrik(Swepub:uu)maing121
(författare)
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Hallbeck, MartinLinköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Klinisk patologi och klinisk genetik,Linkoping Univ, Dept Clin Pathol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.(Swepub:liu)marha90
(författare)
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Linköpings universitetAvdelningen för neuro- och inflammationsvetenskap
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Ingår i:Plos One: Public Library of Science (PLoS)11:121932-6203
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