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Modulation of α-syn...
Modulation of α-synuclein fibrillization by ring-fused 2-pyridones : templation and inhibition involve oligomers with different structure
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- Horvath, Istvan (author)
- Umeå universitet,Kemiska institutionen
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- Sellstedt, Magnus (author)
- Umeå universitet,Kemiska institutionen
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- Weise, Christoph (author)
- Umeå universitet,Kemiska institutionen
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- Nordvall, Lina-Maria (author)
- Umeå universitet,Kemiska institutionen
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- Golla, Krishna Prasad (author)
- Umeå universitet,Kemiska institutionen
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- Olofsson, Anders (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Larsson, Göran (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Almqvist, Fredrik (author)
- Umeå universitet,Kemiska institutionen
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- Wittung-Stafshede, Pernilla (author)
- Umeå universitet,Kemiska institutionen
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(creator_code:org_t)
- Elsevier, 2013
- 2013
- English.
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In: Archives of Biochemistry and Biophysics. - : Elsevier. - 0003-9861 .- 1096-0384. ; 532:2, s. 84-90
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- In a recent study we discovered that a ring-fused 2-pyridone compound triggered fibrillization of a key protein in Parkinson's disease, α-synuclein. To reveal how variations in compound structure affect protein aggregation, we now prepared a number of strategic analogs and tested their effects on α-synuclein amyloid fiber formation in vitro. We find that, in contrast to the earlier templating effect, some analogs inhibit α-synuclein fibrillization. For both templating and inhibiting compounds, the key species formed in the reactions are α-synuclein oligomers that contain compound. Despite similar macroscopic appearance, the templating and inhibiting oligomers are distinctly different in secondary structure content. When the inhibitory oligomers are added in seed amounts, they inhibit fresh α-synuclein aggregation reactions. Our study demonstrates that small chemical changes to the same central fragment can result in opposite effects on protein aggregation.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- α-synuclein
- amyloid
- oligomer
- protein aggregation
- spectroscopy
- 2-pyridone
Publication and Content Type
- ref (subject category)
- art (subject category)
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