Home > Publications Database > Quaternary structure of patient-homogenate amplified α-synuclein fibrils modulates seeding of endogenous α-synuclein. > print

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024 7 _ |a 10.1038/s42003-022-03948-y
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037 _ _ |a DZNE-2022-01554
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Frieg, Benedikt
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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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650 _ 7 |a alpha-Synuclein
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650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Cryoelectron Microscopy
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Multiple System Atrophy: pathology
|2 MeSH
650 _ 2 |a Parkinson Disease
|2 MeSH
650 _ 2 |a Synucleinopathies
|2 MeSH
650 _ 2 |a alpha-Synuclein: chemistry
|2 MeSH
700 1 _ |a Geraets, James A
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700 1 _ |a Strohäker, Timo
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700 1 _ |a Dienemann, Christian
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700 1 _ |a Mavroeidi, Panagiota
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700 1 _ |a Jung, Byung Chul
|0 0000-0003-0732-0122
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700 1 _ |a Kim, Woojin S
|0 0000-0002-4707-933X
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700 1 _ |a Lee, Seung-Jae
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700 1 _ |a Xilouri, Maria
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700 1 _ |a Zweckstetter, Markus
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700 1 _ |a Schröder, Gunnar F
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773 _ _ |a 10.1038/s42003-022-03948-y
|g Vol. 5, no. 1, p. 1040
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|t Communications biology
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|y 2022
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856 4 _ |y OpenAccess
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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