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SOD1 aggregation in ALS mice shows simplistic test tube behavior
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
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2015 (Engelska)Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, nr 32, s. 9878-9883Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

A longstanding challenge in studies of neurodegenerative disease has been that the pathologic protein aggregates in live tissue are not amenable to structural and kinetic analysis by conventional methods. The situation is put in focus by the current progress in demarcating protein aggregation in vitro, exposing new mechanistic details that are now calling for quantitative in vivo comparison. In this study, we bridge this gap by presenting a direct comparison of the aggregation kinetics of the ALS-associated protein superoxide dismutase 1 (SOD1) in vitro and in transgenic mice. The results based on tissue sampling by quantitative antibody assays show that the SOD1 fibrillation kinetics in vitro mirror with remarkable accuracy the spinal cord aggregate buildup and disease progression in transgenic mice. This similarity between in vitro and in vivo data suggests that, despite the complexity of live tissue, SOD1 aggregation follows robust and simplistic rules, providing new mechanistic insights into the ALS pathology and organism-level manifestation of protein aggregation phenomena in general.

Ort, förlag, år, upplaga, sidor
2015. Vol. 112, nr 32, s. 9878-9883
Nyckelord [en]
superoxide dismutase 1, aggregation, transgenic mice, aggregation kinetics
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:umu:diva-108139DOI: 10.1073/pnas.1503328112ISI: 000359285100046PubMedID: 26221023OAI: oai:DiVA.org:umu-108139DiVA, id: diva2:855111
Tillgänglig från: 2015-09-18 Skapad: 2015-09-04 Senast uppdaterad: 2018-06-07Bibliografiskt granskad

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Zetterström, PerBrännström, ThomasMarklund, Stefan L.

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Zetterström, PerBrännström, ThomasMarklund, Stefan L.
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Proceedings of the National Academy of Sciences of the United States of America
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Totalt: 210 träffar
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