Table 2. Effects of pharmacological proteostasis network (PN) modifiers on animal models of neurodegenerative disease.
Compound | Effect on PN | Disease model | Effect | Reference |
---|---|---|---|---|
Radicicol | Activates HSF1 | HD mouse brain slices | Delays aggregation | 64 |
Geldanamycin | Activates HSF1 | PD flies | Suppresses loss of dopaminergic neurons | 135 |
17-AAG | Activates HSF1 | SCA3/MJD flies | Suppresses compound eye degeneration and SCA3 aggregation, improves survival | 134 |
17-AAG | Activates HSF1 | HD flies | Suppresses degeneration of photoreceptor neurons | 134 |
HSP990 | Activates HSF1 | HD mice | Transiently suppresses aggregation and motor decline | 95 |
Arimoclomol | Coactivates HSF1 | ALS mice (G93A) | Suppresses motor neuron death, rescues hind-limb function, and increases life span | 179 |
NG-094 | Coactivates HSF1 | Worms expressing polyQ in body wall | Reduces aggregation and suppresses motility defects | 180 |
Dexamethasone | Increases HSF1 levels | HD mice | Suppresses aggregation and improves motor performance | 97 |
Dexamethasone | Increases HSF1 levels | HD flies | Suppresses aggregation and improves behavioral phenotypes | 97 |
Geranylgeranyl-acetone | Increases HSP70 levels | SBMA mice | Suppresses aggregation and muscle wasting and improves motor function | 181 |
HSF1A | Activates HSF1 | SCA3/MJD flies | Restores eye morphology, size, and pigment color | 137 |
F1 | Activates multiple stress responses | Worms expressing polyQ in body wall muscle | Suppresses aggregation and movement defects | 136 |
Rapamycin | Increases autophagy | HD flies | Suppresses photoreceptor neuron death | 141 |
CCI-779 (rapamycin ester) | Increases autophagy | HD mice | Reduces striatal aggregation and improves motor function | 141 |
SMER10 | Increases autophagy | HD flies | Suppresses photoreceptor neuron degeneration | 146 |
SMER18 | Increases autophagy | HD flies | Suppresses photoreceptor neuron degeneration | 146 |
SMER28 | Increases autophagy | HD flies | Suppresses photoreceptor neuron degeneration | 146 |
Verapamil | Increases autophagy | HD zebrafish | Reduces aggregation and restores rhodopsin expression | 182 |
Clonidine | Increases autophagy | HD zebrafish | Reduces aggregation and restores rhodopsin expression | 182 |
Abbreviations: ALS, amyotrophic lateral sclerosis; HD, Huntington's disease; HSF1, heat shock factor 1; PD, Parkinsons disease; SBMA, spinobulbar muscular atrophy; polyQ, polyglutamine; SMER, small-molecule enhancer of rapamycin.