path(HBP:proteotoxicity)
Genetic approaches using these disease models demonstrate that the chaperome plays a crucial role in protecting cells from proteotoxicity. PubMed:27491084
Although HSP70 was not identified as a modifier of α -synuclein in the screen studies we selected, directed overexpression of HSP70 has been shown to reduce α -synuclein-related proteotoxicity, supporting a central role for HSP70 in diseases of protein misfolding (Auluck et al., 2002). PubMed:27491084
Multiple studies in model systems demonstrate that overexpression of HSP70 can reduce toxicity and protein aggregation. PubMed:27491084
In addition to co-chaperones, overexpression of the human sHSP (HSPB7), a Caenorhabditis elegans HSP100 homolog (tor-2), and the yeast HSP60 subunit (CCT-1) and HSP90 homolog (HSP82) reduced toxicity and aggregation (Cao et al., 2005; Tam et al., 2006; Liang et al., 2008; Vos et al., 2010). PubMed:27491084
In addition to co-chaperones, overexpression of the human sHSP (HSPB7), a Caenorhabditis elegans HSP100 homolog (tor-2), and the yeast HSP60 subunit (CCT-1) and HSP90 homolog (HSP82) reduced toxicity and aggregation (Cao et al., 2005; Tam et al., 2006; Liang et al., 2008; Vos et al., 2010). PubMed:27491084
In addition to co-chaperones, overexpression of the human sHSP (HSPB7), a Caenorhabditis elegans HSP100 homolog (tor-2), and the yeast HSP60 subunit (CCT-1) and HSP90 homolog (HSP82) reduced toxicity and aggregation (Cao et al., 2005; Tam et al., 2006; Liang et al., 2008; Vos et al., 2010). PubMed:27491084
Likewise, overexpression of the yeast TPR-domain-containing co- chaperone STI1 suppresses toxicity in a yeast model expressing the expanded huntingtin fragment (Wolfe et al., 2013). PubMed:27491084
The co- chaperone HSP40 (dHdj-1 and SIS1) and the nucleotide exchange factor SSE1 that specifically modulate HSP70 activity were also shown to suppress toxicity and aggregation in yeast and fly disease models (Chan et al., 2000; Krobitsch and Lindquist, 2000; Sadlish et al., 2008). PubMed:27491084
In addition to co-chaperones, overexpression of the human sHSP (HSPB7), a Caenorhabditis elegans HSP100 homolog (tor-2), and the yeast HSP60 subunit (CCT-1) and HSP90 homolog (HSP82) reduced toxicity and aggregation (Cao et al., 2005; Tam et al., 2006; Liang et al., 2008; Vos et al., 2010). PubMed:27491084
For this purpose, we focused on the well-characterized DK280 mutation (10–13), which specifically leads to aggregation-mediated toxicity. PubMed:22611162
BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.
If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.