Table 2.
Summary of studies examining effects of HDAC6 inhibition in the nervous system.
| Study Model | HDAC6 Modulation | Effect of HDAC6 Inhibition | Citation |
|---|---|---|---|
| Mouse cortical neurons | Genetic and pharmacological (Trichostatin A) | Increased survival and regeneration in setting of oxidative stress. | Rivieccio et al. (2009) [24] |
| Mouse cortical neurons | Trichostatin A Scriptaid | Protection of kainic acid-induced axonal degeneration. | Hanson et al. (2018) [25] |
| SOD1G93A ALS mouse model | HDAC6 deletion | Buildup of SOD1G93A aggregates but only mild effects on motor function. | Lee et al. (2015) [33] |
| SOD1G93A ALS mouse model | HDAC6 deletion | Decrease in disease progression and prolonged survival. | Taes et al. (2013) [34] |
| APP/PS1 mouse model | HDAC6 deletion | Improvement in memory function | Govindarajan et al. (2013) [38] |
| rTg4510 mouse model | Tubastatin A | Improvement in memory function and lower tau levels | Selenica et al. (2014) [39] |
| AD mouse model | Tubastatin A ACY-1215 | Improvement in behavior and decrease in amyloid β and hyperphosphorylated tau. | Zhang et al. (2014) [40] |
| AD mouse model | MPT0G211 | Improvement in learning and memory and decrease in tau phosphorylation. | Fan et al. (2018) [42] |
| Charcot-Marie-Tooth HSPB1 mouse model | ACY-738 ACY-775 |
Rescue of axonal transport deficits | Benoy et al. (2017) [43] |
| Charcot-Marie-Tooth GARS mouse model | Tubastatin A | Improved deficits in axonal transport & motor functioning | Shen et al. (2016) [44] |
| Cortical neurons from MECP2T158A mouse model | Tubastatin A | Increased α-tubulin acetylation | Gold et al. (2015) [48] |
| Rett syndrome patient fibroblast | Tubastatin A | Ameliorated microtubule defects | Gold et al. (2015) [48] |
| Cultured rat oligodendrocytes | Tubastatin A shRNA |
Reduced microtubule binding activity of tau. Reduced protein aggregation. |
Noack et al. (2014) [51] Leyk et al. (2015) [52] |
| dyeucd6 zebrafish model | Tubastatin A | Rescued visual function and retinal morphology | Leyk et al. (2017) [53] |
| Motor neurons from iPSCs of CMT2F and dHMN2B patients | CHEMICAL X4 CHEMICAL X9 |
Reversed axonal movement defects of mitochondria | Kim et al. (2015) [75] |
| Motor neurons from iPSCs of FUS-ALS patients | ACY-738 Tubastatin A Antisense oligos |
Restore axonal transport defects and increase mitochondria-ER overlay | Guo et al. (2017) [76] |
| Neurons from iPSCs of Rett syndrome patients with MECP2 mutations | ACY-1215 | Reversal of decrease in α-tubulin acetylation | Landucci et al. (2018) [77] |