![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB |
![[thumbnail of Supplementary Material]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Material)
11MB |
| Item Type: | Article |
|---|---|
| Title: | Small, seeding-competent huntingtin fibrils are prominent aggregate species in brains of zQ175 Huntington's disease knock-in mice |
| Creators Name: | Schindler, F., Praedel, N., Neuendorf, N., Kunz, S., Schnoegl, S., Mason, M.A., Taxy, B.A., Bates, G.P., Khoshnan, A., Priller, J., Grimm, J., Maier, M., Boeddrich, A. and Wanker, E.E. |
| Abstract: | The deposition of mutant huntingtin (mHTT) protein aggregates in neurons of patients is a pathological hallmark of Huntington’s disease (HD). Previous investigations in cell-free and cell-based disease models showed mHTT exon-1 (mHTTex1) fragments with pathogenic polyglutamine (polyQ) tracts (>40 glutamines) to self-assemble into highly stable, β-sheet-rich protein aggregates with a fibrillar morphology. HD knock-in mouse models have not been extensively studied with regard to mHTT aggregation. They endogenously produce full-length mHTT with a pathogenic polyQ tract as well as mHTTex1 fragments. Here, we demonstrate that seeding-competent, fibrillar mHTT aggregates can be readily detected in brains of zQ175 knock-in HD mice. To do this, we applied a highly sensitive FRET-based protein amplification assay that is capable of detecting seeding-competent mHTT aggregate species down to the femtomolar range. Furthermore, we show that fibrillar structures with an average length of ∼200 nm can be enriched with aggregate-specific mouse and human antibodies from zQ175 mouse brain extracts through immunoprecipitations, confirming that such structures are formed in vivo. Together these studies indicate that small, fibrillar, seeding-competent mHTT structures are prominent aggregate species in brains of zQ175 mice. |
| Keywords: | Huntington's Disease, Aggregates, Seeding, mHTT, zQ175, Brain, Protein Misfolding, FRASE Assay, Animals, Mice |
| Source: | Frontiers in Neuroscience |
| ISSN: | 1662-453X |
| Publisher: | Frontiers Media SA |
| Volume: | 15 |
| Page Range: | 682172 |
| Date: | 22 June 2021 |
| Official Publication: | https://doi.org/10.3389/fnins.2021.682172 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
