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| Hauptseite > Publikationsdatenbank > Quaternary structure of patient-homogenate amplified α-synuclein fibrils modulates seeding of endogenous α-synuclein > print |
| Hauptseite > Publikationsdatenbank > Quaternary structure of patient-homogenate amplified α-synuclein fibrils modulates seeding of endogenous α-synuclein > print |
| 001 | 912258 | ||
| 005 | 20230308123146.0 | ||
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| 100 | 1 | _ | |a Frieg, Benedikt |0 P:(DE-Juel1)172887 |b 0 |u fzj |
| 245 | _ | _ | |a Quaternary structure of patient-homogenate amplified α-synuclein fibrils modulates seeding of endogenous α-synuclein |
| 260 | _ | _ | |a London |c 2022 |b Springer Nature |
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| 520 | _ | _ | |a Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are progressive and unremitting neurological diseases that are neuropathologically characterized by α-synuclein inclusions. Increasing evidence supports the aggregation of α-synuclein in specific brain areas early in the disease course, followed by the spreading of α-synuclein pathology to multiple brain regions. However, little is known about how the structure of α-synuclein fibrils influence its ability to seed endogenous α-synuclein in recipient cells. Here, we aggregated α-synuclein by seeding with homogenates of PD- and MSA-confirmed brain tissue, determined the resulting α-synuclein fibril structures by cryo-electron microscopy, and characterized their seeding potential in mouse primary oligodendroglial cultures. The combined analysis shows that the two patient material-amplified α-synuclein fibrils share a similar protofilament fold but differ in their inter-protofilament interface and their ability to recruit endogenous α-synuclein. Our study indicates that the quaternary structure of α-synuclein fibrils modulates the seeding of α-synuclein pathology inside recipient cells. It thus provides an important advance in the quest to understand the connection between the structure of α-synuclein fibrils, cellular seeding/spreading, and ultimately the clinical manifestations of different synucleinopathies. |
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| 700 | 1 | _ | |a Geraets, James A. |0 P:(DE-Juel1)176479 |b 1 |u fzj |
| 700 | 1 | _ | |a Strohäker, Timo |0 P:(DE-HGF)0 |b 2 |
| 700 | 1 | _ | |a Dienemann, Christian |0 0000-0002-2172-5110 |b 3 |
| 700 | 1 | _ | |a Mavroeidi, Panagiota |0 P:(DE-HGF)0 |b 4 |
| 700 | 1 | _ | |a Jung, Byung Chul |0 0000-0003-0732-0122 |b 5 |
| 700 | 1 | _ | |a Kim, Woojin S. |0 0000-0002-4707-933X |b 6 |
| 700 | 1 | _ | |a Lee, Seung-Jae |0 P:(DE-HGF)0 |b 7 |
| 700 | 1 | _ | |a Xilouri, Maria |0 P:(DE-HGF)0 |b 8 |
| 700 | 1 | _ | |a Zweckstetter, Markus |0 0000-0002-2536-6581 |b 9 |e Corresponding author |
| 700 | 1 | _ | |a Schröder, Gunnar F. |0 P:(DE-Juel1)132018 |b 10 |e Corresponding author |
| 773 | _ | _ | |a 10.1038/s42003-022-03948-y |g Vol. 5, no. 1, p. 1040 |0 PERI:(DE-600)2919698-X |n 1 |p 1040 |t Communications biology |v 5 |y 2022 |x 2399-3642 |
| 856 | 4 | _ | |u https://juser.fz-juelich.de/record/912258/files/1200186598_MPDL_Rechnung.pdf |
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