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| Item Type: | Review |
|---|---|
| Title: | Spontaneous self-assembly of pathogenic huntingtin exon 1 protein into amyloid structures |
| Creators Name: | Trepte, P. and Strempel, N. and Wanker, E.E. |
| Abstract: | PolyQ (polyglutamine) diseases such as HD (Huntington's disease) or SCA1 (spinocerebellar ataxia type 1) are neurodegenerative disorders caused by abnormally elongated polyQ tracts in human proteins. PolyQ expansions promote misfolding and aggregation of disease-causing proteins, leading to the appearance of nuclear and cytoplasmic inclusion bodies in patient neurons. Several lines of experimental evidence indicate that this process is critical for disease pathogenesis. However, the molecular mechanisms underlying spontaneous polyQ-containing aggregate formation and the perturbation of neuronal processes are still largely unclear. The present chapter reviews the current literature regarding misfolding and aggregation of polyQ-containing disease proteins. We specifically focus on studies that have investigated the amyloidogenesis of polyQ-containing HTTex1 (huntingtin exon 1) fragments. These protein fragments are disease-relevant and play a critical role in HD pathogenesis. We outline potential mechanisms behind mutant HTTex1 aggregation and toxicity, as well as proteins and small molecules that can modify HTTex1 amyloidogenesis in vitro and in vivo. The potential implications of such studies for the development of novel therapeutic strategies are discussed. |
| Keywords: | Amyloid, Exons, Huntington Disease, Mutation, Nerve Tissue Proteins, Pathological Protein Aggregation, Peptides, Protein Folding, Protein Multimerization, Animals |
| Source: | Essays in Biochemistry |
| ISSN: | 0071-1365 |
| Publisher: | Portland Press |
| Volume: | 56 |
| Number: | 1 |
| Page Range: | 167-180 |
| Date: | 18 August 2014 |
| Official Publication: | https://doi.org/10.1042/bse0560167 |
| PubMed: | View item in PubMed |
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