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000912258 1001_ $$0P:(DE-Juel1)172887$$aFrieg, Benedikt$$b0$$ufzj
000912258 245__ $$aQuaternary structure of patient-homogenate amplified α-synuclein fibrils modulates seeding of endogenous α-synuclein
000912258 260__ $$aLondon$$bSpringer Nature$$c2022
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000912258 520__ $$aParkinson’s disease (PD) and Multiple System Atrophy (MSA) are progressive and unremitting neurological diseases that are neuropathologically characterized by α-synuclein inclusions. Increasing evidence supports the aggregation of α-synuclein in specific brain areas early in the disease course, followed by the spreading of α-synuclein pathology to multiple brain regions. However, little is known about how the structure of α-synuclein fibrils influence its ability to seed endogenous α-synuclein in recipient cells. Here, we aggregated α-synuclein by seeding with homogenates of PD- and MSA-confirmed brain tissue, determined the resulting α-synuclein fibril structures by cryo-electron microscopy, and characterized their seeding potential in mouse primary oligodendroglial cultures. The combined analysis shows that the two patient material-amplified α-synuclein fibrils share a similar protofilament fold but differ in their inter-protofilament interface and their ability to recruit endogenous α-synuclein. Our study indicates that the quaternary structure of α-synuclein fibrils modulates the seeding of α-synuclein pathology inside recipient cells. It thus provides an important advance in the quest to understand the connection between the structure of α-synuclein fibrils, cellular seeding/spreading, and ultimately the clinical manifestations of different synucleinopathies.
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000912258 7001_ $$0P:(DE-Juel1)176479$$aGeraets, James A.$$b1$$ufzj
000912258 7001_ $$0P:(DE-HGF)0$$aStrohäker, Timo$$b2
000912258 7001_ $$00000-0002-2172-5110$$aDienemann, Christian$$b3
000912258 7001_ $$0P:(DE-HGF)0$$aMavroeidi, Panagiota$$b4
000912258 7001_ $$00000-0003-0732-0122$$aJung, Byung Chul$$b5
000912258 7001_ $$00000-0002-4707-933X$$aKim, Woojin S.$$b6
000912258 7001_ $$0P:(DE-HGF)0$$aLee, Seung-Jae$$b7
000912258 7001_ $$0P:(DE-HGF)0$$aXilouri, Maria$$b8
000912258 7001_ $$00000-0002-2536-6581$$aZweckstetter, Markus$$b9$$eCorresponding author
000912258 7001_ $$0P:(DE-Juel1)132018$$aSchröder, Gunnar F.$$b10$$eCorresponding author
000912258 773__ $$0PERI:(DE-600)2919698-X$$a10.1038/s42003-022-03948-y$$gVol. 5, no. 1, p. 1040$$n1$$p1040$$tCommunications biology$$v5$$x2399-3642$$y2022
000912258 8564_ $$uhttps://juser.fz-juelich.de/record/912258/files/1200186598_MPDL_Rechnung.pdf
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