Table 2.
Some examples of the effects of histone deacetylase inhibitors (HDACi) in animal models of neurodegenerative diseases.
| Compound | Experimental model* | Results | References |
|---|---|---|---|
| Sodium butyrate | Transgenic AD mice (CK-p25) | 4 week intra-peritoneal administration improved learning and memory | Fischer et al., 2007 |
| Trichostatin A | Transgenic AD mice (APP/PS1) | Acute treatment prior to fear conditioning training rescued hippocampal H4 acetylation levels and contextual freezing performances | Francis et al., 2009 |
| Sodium butyrate, sodium valproate, or vorinostat | Transgenic AD mice (APP/PS1) | 2–3 weeks intra-peritoneal injection reversed contextual memory deficits | Kilgore et al., 2010 |
| Sodium butyrate | Transgenic AD mice (APP/PS1) | Chronic intra-peritoneal injection improved associative memory | Govindarajan et al., 2011 |
| Sodium butyrate | Transgenic AD mice (Tg2576) | 5 week intra-peritoneal injection decreased tau phosphorylation and restored dendritic spine density in hippocampal neurons | Ricobaraza et al., 2010 |
| MS-275 (entinostat) | Transgenic AD mice (APP/PS1) | 10 days oral administration ameliorated neuroinflammation and cerebral amyloidosis and improved behavior | Zhang and Schluesener, 2013 |
| W2 (Class II HDACi) | Transgenic AD mice (3 × AD) | 4 weeks intra-peritoneal injection improved memory functions and decreased Aβ and phosphorylated tau levels | Sung et al., 2013 |
| Sodium butyrate or vorinostat | Drosophila model of PD overexpressing α-synuclein | 20 days treatment reduced α-synuclein mediated toxicity | Kontopoulos et al., 2006 |
| AK-1 or AGK-2 (sirtuin 2 HDACi) | Drosophila model of PD overexpressing α-synuclein | 20 days treatment reduced α-synuclein mediated toxicity | Outeiro et al., 2007 |
| Valproic acid | Rotenone-induced PD rat model | 4 weeks oral administration counteracted α-synuclein nuclear translocation and toxicity | Monti et al., 2010 |
| Sodium butyrate | MPTP-induced PD mouse model | 14 days oral administration up-regulated DJ-1 expression and reduced neurotoxicity | Zhou et al., 2011 |
| Sodium butyrate | Rat model of PD | 5 days intra-peritoneal injection alleviated cognitive deficits | Rane et al., 2012 |
| Sodium butyrate | Rotenone-induced PD fly model | 3 days oral administration improved locomotor impairment and early mortality | St Laurent et al., 2013 |
| Sodium butyrate, trichostatin A, or valproate | ALS mice (SOD1-G93A) | Several studies show that treatments with one ot those agents delayed disease progression and/or increased animal survival | Sugai et al., 2004; Ryu et al., 2005; Yoo and Ko, 2011 |
| 4b (HDAC1i and HDAC3i) | Transgenic HD mice | 10–12 weeks injections improved motor functions and elicited cognitive decline | Jia et al., 2012 |
| AK-7 (sirtuin 2 HDACi) | Transgenic HD mice | 4 weeks intra-peritoneal injection improved motor functions, extended survival and reduced mutant huntingtin aggregation | Chopra et al., 2012 |
*
Most of the used transgenic models over-expressed mutant proteins (amyloid precursor protein and presenilin 1 in AD APP/PS1 models, α-synuclein in PD models, mutant superoxide dismutase “SOD1” in ALS models, and mutant huntingtin in HD model) or were induced by pesticide exposure (such as rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine “MPTP”). AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; HD, Huntington's disease; PD, Parkinson's disease).