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• W3104618497 abstract "Abstract In Huntington’s disease (HD), the mutant Huntingtin (mHTT) is postulated to mediate template-based aggregation that can propagate across cells. It has been difficult to quantitatively detect such pathological seeding activities in patient biosamples, e.g. cerebrospinal fluids (CSF), and study their correlation with the disease manifestation. Here we developed a cell line expressing a domain-engineered mHTT-exon 1 reporter, which showed remarkably high sensitivity and specificity in detecting mHTT seeding species in HD patient biosamples. We showed that the seeding-competent mHTT species in HD CSF are significantly elevated upon disease onset and with the progression of neuropathological grades. Mechanistically, we showed that mHTT seeding activities in patient CSF could be ameliorated by the overexpression of chaperone DNAJB6 and by antibodies against the polyproline domain of mHTT. Together, our study developed a selective and scalable cell-based tool to investigate mHTT seeding activities in HD CSF, and demonstrated that the CSF mHTT seeding species are significantly associated with certain disease states. This seeding activity can be ameliorated by targeting specific domain or proteostatic pathway of mHTT, providing novel insights into such pathological activities." @default.
• W3104618497 created "2020-11-23" @default.
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• W3104618497 date "2020-11-20" @default.
• W3104618497 modified "2023-10-17" @default.
• W3104618497 title "Disease-related Huntingtin seeding activities in cerebrospinal fluids of Huntington’s disease patients" @default.
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• W3104618497 doi "https://doi.org/10.1038/s41598-020-77164-1" @default.
• W3104618497 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7679413" @default.
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