| First Author | Taes I | Year | 2013 |
| Journal | Hum Mol Genet | Volume | 22 |
| Issue | 9 | Pages | 1783-90 |
| PubMed ID | 23364049 | Mgi Jnum | J:194977 |
| Mgi Id | MGI:5475398 | Doi | 10.1093/hmg/ddt028 |
| Citation | Taes I, et al. (2013) Hdac6 deletion delays disease progression in the SOD1G93A mouse model of ALS. Hum Mol Genet 22(9):1783-90 |
| abstractText | Defects in axonal transport are thought to contribute to the pathogenesis of neurodegenerative disease. Because alpha-tubulin acetylation facilitates axonal transport, inhibition of the alpha-tubulin deacetylating enzymes, histone deacetylase 6 (Hdac6) and silent information regulator 2 (Sirt2), is thought to be an interesting therapeutic strategy for these conditions. Amyotrophic lateral sclerosis (ALS) is a one such rapidly progressive and fatal neurodegenerative disorder, in which axonal transport defects have been found in vitro and in vivo. To establish whether the inhibition of Hdac6 or Sirt2 may be of interest for ALS treatment, we investigated whether deleting Hdac6 or Sirt2 from the superoxide dismutase 1, SOD1(G93A) mouse affects the motor neuron degeneration in this ALS model. Deletion of Hdac6 significantly extended the survival of SOD1(G93A) mice without affecting disease onset, and maintained motor axon integrity. This protective effect was associated with increased alpha-tubulin acetylation. Deletion of Sirt2 failed to affect the disease course, but also did not modify alpha-tubulin acetylation. These findings show that Hdac6, rather than Sirt2, is a therapeutic target for the treatment of ALS. Moreover, Sirt2 appears not to be a major alpha-tubulin deacetylase in the nervous system. |
