Title |
Prion-Like Seeding of Misfolded α-Synuclein in the Brains of Dementia with Lewy Body Patients in RT-QUIC
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Published in |
Molecular Neurobiology, May 2017
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DOI | 10.1007/s12035-017-0624-1 |
Pubmed ID | |
Authors |
Kazunori Sano, Ryuichiro Atarashi, Katsuya Satoh, Daisuke Ishibashi, Takehiro Nakagaki, Yasushi Iwasaki, Mari Yoshida, Shigeo Murayama, Kenichi Mishima, Noriyuki Nishida |
Abstract |
The prion-like seeding of misfolded α-synuclein (αSyn) involved in the pathogenesis of Lewy body diseases (LBD) remains poorly understood at the molecular level. Using the real-time quaking-induced conversion (RT-QUIC) seeding assay, we investigated whether brain tissues from cases of dementia with Lewy bodies (DLB), which contain serine 129 (Ser129)-phosphorylated insoluble aggregates of αSyn, can convert Escherichia coli-derived recombinant αSyn (r-αSyn) to fibrils. Diffuse neocortical DLB yielded 50% seeding dose (SD50) values of 10(7)~10(10)/g brain. Limbic DLB was estimated to have an SD50 value of ~10(5)/g brain. Furthermore, RT-QUIC assay discriminated DLB from other neurological and neurodegenerative disorders. Unexpectedly, the prion-like seeding was reconstructed in reactions seeded with oligomer-like species, but not with insoluble aggregates of r-αSyn, regardless of Ser129 phosphorylation status. Our findings suggest that RT-QUIC using r-αSyn can be applied to detect seeding activity in LBD, and the culprit that causes prion-like seeding may be oligomeric forms of αSyn. |
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Mendeley readers
Geographical breakdown
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Germany | 1 | <1% |
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Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 9 | 8% |
Student > Doctoral Student | 7 | 6% |
Student > Bachelor | 7 | 6% |
Other | 16 | 15% |
Unknown | 23 | 21% |
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Psychology | 4 | 4% |
Other | 9 | 8% |
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