Table 1.
Molecular chaperones as a therapeutic target
| A) Pharmacologic upregulation of molecular chaperones
| ||
|---|---|---|
| Compound | Target | Investigated for: |
| Geldanamycin | Hsp90 Inhibitor | PD [54, 127–129, 133–135] |
| AD [111] | ||
| ALS [139, 140] | ||
| PolyQ disease [136–138, 210] | ||
| 17-AAG | Hsp90 Inhibitor | PD [73, 113, 114, 144, 145] |
| ALS [211] | ||
| PolyQ disease [146, 147, 210, 211] | ||
| 17-DMAG | Hsp90 Inhibitor | PolyQ disease [212] |
| SNX-0723 and others | Hsp90 Inhibitor | PD [144] |
| Arimoclomol | HSF-1 enhancer | ALS [150–152] |
| HSF1A | HSF-1 enhancer | PolyQ disease [159] |
| Celastrol | Hsp70 induction | PD [162, 163] |
| AD [213] | ||
| ALS [164] | ||
| PolyQ disease [165, 166] | ||
| Geranylgeranylacetone (GGA) | Hsp70 induction | PolyQ disease [171] |
| Valproate | Hsp70 induction | PD [176, 177] |
| AD [214] | ||
| ALS [215] | ||
| PolyQ disease [216] | ||
| Trehalose | Direct chaperone function and mTOR independent autophagy induction | PD [184, 185] |
| AD [185, 217, 218] | ||
| ALS [219] | ||
| PolyQ disease [183, 184, 220] | ||
| B) Viral-mediated upregulation of chaperone function | |
|---|---|
| AAV-Hsp70 | MPTP mouse model of PD [191] |
| AAV-CDCrel-1 rat model of PD [193] | |
| AAV-H-BH (constitutively active form of HSF-1) | AAV-CDCrel-1 rat model of PD [193] |
| LV-Hsp104 | LV-(h)A30P α-synuclein rat model of PD [194] |
| AAV-BAG5 (DARA) | MPTP mouse model of PD [88] |
|
| |
| C) Cell-penetrating peptide technology-mediated upregulation of chaperone function
| |
| TAT-Hsp70 | MPTP in cell culture [198] |
| MPTP mouse model of PD [198] | |
AAV (adeno-associated virus); AD (Alzheimer’s disease); ALS (amyotrophic lateral sclerosis); LV (lentivirus); PD (Parkinson’s disease); PolyQ disease (polyglutamine repeat expansion disease); TAT (trans-activator of transcription)