Title: Hdac6 deletion delays disease progression in the SOD1G93A mouse model of ALS
Authors: Taes, Ines
Timmers, Mieke
Hersmus, Nicole
Abreu Bento, André
Van Den Bosch, Ludo
Van Damme, Philip
Auwerx, Johan
Robberecht, Wim # ×
Issue Date: May-2013
Publisher: IRL Press
Series Title: Human molecular genetics vol:22 issue:9 pages:1783-1790
Abstract: Defects in axonal transport are thought to contribute to the pathogenesis of neurodegenerative disease. Because α-tubulin acetylation facilitates axonal transport, inhibition of the α-tubulin deacetylating enzymes, Hdac6 and 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 inhibition of Hdac6 or Sirt2 may be of interest for ALS treatment, we investigated whether deleting Hdac6 or Sirt2 from the 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 α-tubulin acetylation. Deletion of Sirt2 failed to affect the disease course, but did also not modify α-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 α-tubulin deacetylase in the nervous system.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Neurobiology (Vesalius Research Center)
× corresponding author
# (joint) last author

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