Therapeutic potential of HDAC6 in amyotrophic lateral sclerosis

Authors:

Wenting Guo1,2 and Ludo Van Den Bosch1,2
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Affiliations:

1 KU Leuven-Department of Neurosciences, Experimental Neurology, Leuven, Belgium.

2 VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium.

Keywords: 

Histone deacetylase 6, motor neuron, neurodegeneration, acetylation, axonal transport, therapy, mitochondria.

Corresponding Author(s):

Ludo Van Den Bosch, ludo.vandenbosch@kuleuven.vib.be

Conflict of interest statement:

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Please cite this article as:

Wenting Guo and Ludo Van Den Bosch (2017). Therapeutic potential of HDAC6 in amyotrophic lateral sclerosis. Cell Stress 2(1): 14-16. doi: 10.15698/cst2018.01.120

© 2017 Guo and Van Den Bosch. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

Amyotrophic lateral sclerosis (ALS) is the most common fatal motor neuron disease in adults and no effective treatments exist. Mutations in FUS are one of the genetic causes of familial ALS. We used induced pluripotent stem cells (iPSCs) derived from FUS-ALS patients to investigate the pathological mechanism. We observed hypo-excitability, cytoplasmic FUS localization and axonal transport defects of different cargoes in motor neurons differentiated from these iPSCs. Pharmacological inhibition and genetic silencing of histone deacetylase 6 (HDAC6) restored the axonal transport defects. Moreover, the disturbed association between mitochondria and the endoplasmic reticulum (ER) was also reversed by inhibition of HDAC6. The positive effects of HDAC6 inhibition were linked to an increase in the acetylation level of α-tubulin, one of the building blocks of the microtubules. In conclusion, HDAC6 inhibition could be a potential new therapeutic strategy for ALS.