Table 1.
Proteostasis targets tested in HD models.
| Target | Effect | HD models tested | Phenotype improved | Reference |
|---|---|---|---|---|
| mTOR inhibition | Autophagy induction | Cell line, fly, mouse | Cellular toxicity, mHtt aggregation, motor phenotypes, weight gain | Ravikumar et al. (2004), Berger et al. (2006) |
| IMPase inhibition | Autophagy induction | Cell line | Cellular toxicity, mHtt levels | Sarkar et al. (2005) |
| Calpain inhibition | Autophagy induction | Cell line, zebrafish | Cellular toxicity, mHtt aggregation, photoreceptor degeneration | Williams et al. (2008) |
| I1R activation | Autophagy induction | Cell line, zebrafish, mouse | mHtt aggregation, photoreceptor degeneration, mHtt levels, motor phenotypes | Williams et al. (2008), Rose et al. (2010) |
| L-type Ca2+ channel inhibition | Autophagy induction | Zebrafish | mHtt aggregation, photoreceptor degeneration | Williams et al. (2008) |
| AMPK activation | Autophagy induction | Mouse | Motor phenotypes, survival time | Ma et al. (2007) |
| Hsp40 overexpression | Chaperone induction | Yeast, in vitro | mHtt aggregation, mHtt fibril and oligomer formation | Krobitsch and Lindquist (2000), Muchowski et al. (2000), Wacker et al. (2004) |
| Hsp70 overexpression | Chaperone induction | Yeast, in vitro, fly | mHtt aggregation, mHtt fibril and oligomer formation, ocular degeneration | Warrick et al. (1999), Krobitsch and Lindquist (2000), Muchowski et al. (2000), Wacker et al. (2004) |
| Hsp104 overexpression | Chaperone induction | Cell line, yeast, mouse | Cell death, mHtt aggregation, mouse survival | Carmichael et al. (2000), Krobitsch and Lindquist (2000), Vacher et al. (2005) |
| Hsp90 inhibition | HSF1 and HSR activation | Cell line, fly | mHtt aggregation, photoreceptor degeneration | Sittler et al. (2001), Fujikake et al. (2008) |
| HSF1 activation (Hsp90-independent) | HSR activation | Cell line, fly | mHtt aggregation and levels, cell death, eye degeneration | Neef et al. (2010) |
| Parkin overexpression | UPS induction | Cell line | PolyQ aggregation and levels | Tsai et al. (2003) |
| HRD1 overexpression | UPS induction | Cell line | mHtt levels and aggregation, cell death | Yang et al. (2007) |
| PA28γ overexpression | UPS induction | Primary neuron | mHtt levels, cell death | Seo et al. (2007) |
| CHIP overexpression | UPS induction | Cell line | mHtt aggregation, cell death | Jana et al. (2005) |