The role of histone deacetylase 6 (HDAC6) in neurodegeneration

Abstract

HDAC6 is an enzyme that regulates a variety of biological pathways in dividing cells, but also in post-mitotic neurons. In these cells, different cellular functions and survival are dependent on HDAC6-mediated processes such as intracellular trafficking, antioxidation, chaperone-mediated stress responses, and protein degradation. As a consequence, the interest in HDAC6 as a potential target to treat several neurodegenerative disorders has grown signifi-cantly over the last decade. This review summarizes the current knowledge on the interaction partners and functions of HDAC6 as well as the most important arguments for its involvement in several neurodegenerative diseases. As many of these disorders are hallmarked by alterations in HDAC6-mediated pathways, it is hypothesized that HDAC6 could play a pivotal role in the pathophysiology of neurodegeneration. HDAC6-dependent deacetylation of its substrates could result in neurotoxicity, while the ubiquitin-dependent functions of HDAC6 could be essential for neuroprotection. Therefore, targeting the deacetylating activity of HDAC6, while leaving its other functions unhampered, might be an interesting strategy to treat neurodegenerative disorders.