Home > Publications Database > Structural heterogeneity of α-synuclein fibrils amplified from patient brain extracts. > print

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024 7 _ |a 10.1038/s41467-019-13564-w
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037 _ _ |a DZNE-2020-07974
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Strohäker, Timo
|0 P:(DE-2719)2812850
|b 0
|e First author
245 _ _ |a Structural heterogeneity of α-synuclein fibrils amplified from patient brain extracts.
260 _ _ |a [London]
|c 2019
|b Nature Publishing Group UK
264 _ 1 |3 online
|2 Crossref
|b Springer Science and Business Media LLC
|c 2019-12-04
264 _ 1 |3 print
|2 Crossref
|b Springer Science and Business Media LLC
|c 2019-12-01
336 7 _ |a article
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520 _ _ |a Parkinson's disease (PD) and Multiple System Atrophy (MSA) are clinically distinctive diseases that feature a common neuropathological hallmark of aggregated α-synuclein. Little is known about how differences in α-synuclein aggregate structure affect disease phenotype. Here, we amplified α-synuclein aggregates from PD and MSA brain extracts and analyzed the conformational properties using fluorescent probes, NMR spectroscopy and electron paramagnetic resonance. We also generated and analyzed several in vitro α-synuclein polymorphs. We found that brain-derived α-synuclein fibrils were structurally different to all of the in vitro polymorphs analyzed. Importantly, there was a greater structural heterogeneity among α-synuclein fibrils from the PD brain compared to those from the MSA brain, possibly reflecting on the greater variability of disease phenotypes evident in PD. Our findings have significant ramifications for the use of non-brain-derived α-synuclein fibrils in PD and MSA studies, and raise important questions regarding the one disease-one strain hypothesis in the study of α-synucleinopathies.
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542 _ _ |i 2019-12-01
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|u https://creativecommons.org/licenses/by/4.0
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650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Models, Molecular
|2 MeSH
650 _ 2 |a Multiple System Atrophy: diagnosis
|2 MeSH
650 _ 2 |a Multiple System Atrophy: metabolism
|2 MeSH
650 _ 2 |a Parkinson Disease: diagnosis
|2 MeSH
650 _ 2 |a Parkinson Disease: metabolism
|2 MeSH
650 _ 2 |a Protein Aggregation, Pathological: metabolism
|2 MeSH
650 _ 2 |a Protein Conformation
|2 MeSH
650 _ 2 |a Synucleinopathies: diagnosis
|2 MeSH
650 _ 2 |a Synucleinopathies: metabolism
|2 MeSH
650 _ 2 |a Tissue Extracts: metabolism
|2 MeSH
650 _ 2 |a alpha-Synuclein: chemistry
|2 MeSH
650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
700 1 _ |a Jung, Byung Chul
|b 1
700 1 _ |a Liou, Shu-Hao
|b 2
700 1 _ |a Fernandez, Claudio O
|b 3
700 1 _ |a Riedel, Dietmar
|b 4
700 1 _ |a Becker, Stefan
|b 5
700 1 _ |a Halliday, Glenda M
|b 6
700 1 _ |a Bennati, Marina
|b 7
700 1 _ |a Kim, Woojin S
|b 8
700 1 _ |a Lee, Seung-Jae
|b 9
700 1 _ |a Zweckstetter, Markus
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773 1 8 |a 10.1038/s41467-019-13564-w
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|t Nature Communications
|v 10
|y 2019
|x 2041-1723
773 _ _ |a 10.1038/s41467-019-13564-w
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|t Nature Communications
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856 4 _ |y OpenAccess
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