Unknown

Dataset Information

0

Prion-Like Seeding of Misfolded α-Synuclein in the Brains of Dementia with Lewy Body Patients in RT-QUIC.


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 107~1010/g brain. Limbic DLB was estimated to have an SD50 value of ~105/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.

SUBMITTER: Sano K 

PROVIDER: S-EPMC5884914 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC6801172 | biostudies-literature
| S-EPMC4885095 | biostudies-literature
| S-EPMC8518528 | biostudies-literature
| S-EPMC8373970 | biostudies-literature
| S-EPMC7299922 | biostudies-literature
| S-EPMC9219141 | biostudies-literature
2024-09-18 | GSE235914 | GEO
| S-EPMC4693622 | biostudies-literature
| S-EPMC6686411 | biostudies-literature
| S-EPMC8226794 | biostudies-literature