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| Home > Publications Database > An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils. > print |
| 001 | 140939 | ||
| 005 | 20240430120016.0 | ||
| 024 | 7 | _ | |a 10.7554/eLife.46112 |2 doi |
| 024 | 7 | _ | |a pmid:31389332 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC6721797 |2 pmc |
| 024 | 7 | _ | |a altmetric:64743599 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-07261 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 600 |
| 100 | 1 | _ | |a Agerschou, Emil Dandanell |0 P:(DE-HGF)0 |b 0 |
| 245 | _ | _ | |a An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils. |
| 260 | _ | _ | |a Cambridge |c 2019 |b eLife Sciences Publications |
| 264 | _ | 1 | |3 online |2 Crossref |b eLife Sciences Publications, Ltd |c 2019-08-21 |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1714392905_21079 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Removing or preventing the formation of [Formula: see text]-synuclein aggregates is a plausible strategy against Parkinson's disease. To this end, we have engineered the [Formula: see text]-wrapin AS69 to bind monomeric [Formula: see text]-synuclein with high affinity. In cultured cells, AS69 reduced the self-interaction of [Formula: see text]-synuclein and formation of visible [Formula: see text]-synuclein aggregates. In flies, AS69 reduced [Formula: see text]-synuclein aggregates and the locomotor deficit resulting from [Formula: see text]-synuclein expression in neuronal cells. In biophysical experiments in vitro, AS69 highly sub-stoichiometrically inhibited both primary and autocatalytic secondary nucleation processes, even in the presence of a large excess of monomer. We present evidence that the AS69-[Formula: see text]-synuclein complex, rather than the free AS69, is the inhibitory species responsible for sub-stoichiometric inhibition of secondary nucleation. These results represent a new paradigm that high affinity monomer binders can lead to strongly sub-stoichiometric inhibition of nucleation processes. |
| 536 | _ | _ | |a 342 - Disease Mechanisms and Model Systems (POF3-342) |0 G:(DE-HGF)POF3-342 |c POF3-342 |f POF III |x 0 |
| 542 | _ | _ | |i 2019-08-21 |2 Crossref |u http://creativecommons.org/licenses/by/4.0/ |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 2 | |a Amyloid: antagonists & inhibitors |2 MeSH |
| 650 | _ | 2 | |a HEK293 Cells |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Protein Aggregation, Pathological |2 MeSH |
| 650 | _ | 2 | |a Protein Multimerization: drug effects |2 MeSH |
| 650 | _ | 2 | |a Recombinant Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a Recombinant Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a alpha-Synuclein: metabolism |2 MeSH |
| 700 | 1 | _ | |a Flagmeier, Patrick |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Saridaki, Theodora |0 P:(DE-HGF)0 |b 2 |
| 700 | 1 | _ | |a Galvagnion, Céline |0 P:(DE-2719)2811987 |b 3 |u dzne |
| 700 | 1 | _ | |a Komnig, Daniel |0 P:(DE-HGF)0 |b 4 |
| 700 | 1 | _ | |a Heid, Laetitia |0 P:(DE-HGF)0 |b 5 |
| 700 | 1 | _ | |a Prasad, Vibha |0 P:(DE-HGF)0 |b 6 |
| 700 | 1 | _ | |a Shaykhalishahi, Hamed |0 P:(DE-HGF)0 |b 7 |
| 700 | 1 | _ | |a Willbold, Dieter |0 P:(DE-HGF)0 |b 8 |
| 700 | 1 | _ | |a Dobson, Christopher M |0 P:(DE-HGF)0 |b 9 |
| 700 | 1 | _ | |a Voigt, Aaron |0 P:(DE-HGF)0 |b 10 |
| 700 | 1 | _ | |a Falkenburger, Bjoern |0 P:(DE-HGF)0 |b 11 |
| 700 | 1 | _ | |a Hoyer, Wolfgang |0 P:(DE-HGF)0 |b 12 |
| 700 | 1 | _ | |a Buell, Alexander K |0 P:(DE-HGF)0 |b 13 |e Corresponding author |
| 773 | 1 | 8 | |a 10.7554/elife.46112 |b : eLife Sciences Publications, Ltd, 2019-08-21 |3 journal-article |2 Crossref |t eLife |v 8 |y 2019 |x 2050-084X |
| 773 | _ | _ | |a 10.7554/eLife.46112 |g Vol. 8, p. e46112 |0 PERI:(DE-600)2687154-3 |q 8 |t eLife |v 8 |y 2019 |x 2050-084X |
| 856 | 4 | _ | |y OpenAccess |u https://pub.dzne.de/record/140939/files/DZNE-2020-07261.pdf |
| 856 | 4 | _ | |y OpenAccess |x pdfa |u https://pub.dzne.de/record/140939/files/DZNE-2020-07261.pdf?subformat=pdfa |
| 856 | 7 | _ | |2 Pubmed Central |u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721797 |
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| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 3 |6 P:(DE-2719)2811987 |
| 913 | 1 | _ | |a DE-HGF |b Gesundheit |l Erkrankungen des Nervensystems |1 G:(DE-HGF)POF3-340 |0 G:(DE-HGF)POF3-342 |3 G:(DE-HGF)POF3 |2 G:(DE-HGF)POF3-300 |4 G:(DE-HGF)POF |v Disease Mechanisms and Model Systems |x 0 |
| 914 | 1 | _ | |y 2019 |
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| 915 | _ | _ | |a Creative Commons Attribution CC BY (No Version) |0 LIC:(DE-HGF)CCBYNV |2 V:(DE-HGF) |b DOAJ |
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| 920 | 1 | _ | |0 I:(DE-2719)1013008 |k AG Di Monte |l Neurodegeneration and Neuroprotection in Parkinson´s Disease |x 0 |
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