Recent years have witnessed an emergence of a new class of therapeutic agents, termed histone deacetylase 6 (HDAC6) inhibitors. HDAC6 is one isoform of a family of HDAC enzymes that catalyse the removal of functional acetyl groups from proteins. It stands out from its cousins in almost exclusively deacetylating cytoplasmic proteins, in exerting deacetylation-independent effects and in the success that has been achieved in developing relatively isoform-specific inhibitors of its enzymatic action that have reached clinical trial. HDAC6 plays a pivotal role in the removal of misfolded proteins and it is this role that has been most successfully targeted to date. HDAC6 inhibitors are being investigated for use in combination with proteasome inhibitors for the treatment of lymphoid malignancies, whereby HDAC6-dependent protein disposal currently limits the cytotoxic effectiveness of the latter. Similarly, numerous recent studies have linked altered HDAC6 activity to the pathogenesis of neurodegenerative diseases that are characterized by misfolded protein accumulation. It seems likely though that the function of HDAC6 is not limited to malignancy and neurodegeneration, the deacetylase being implicated in a number of other cellular processes and diseases including in cardiovascular disease, inflammation, renal fibrosis and cystogenesis. Here, we review the unique features of HDAC6 that make it so appealing as a drug target and its currently understood role in health and disease. Whether HDAC6 inhibition will ultimately find a clinical niche in the treatment of malignancy or prevalent complex chronic diseases remains to be determined.
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June 2016
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Mitochondrial protein quality control plays a decisive role in the maintenance of a proper mitochondrial function in metabolically active tissues such as skeletal muscle. Several chaperones and proteases, involved in the regulation of mitochondrial protein quality control, are altered in obesity and type 2 diabetes mellitus. For further details see Dahlmans et al. pp. 843–852.
Review Article|
May 06 2016
The therapeutic hope for HDAC6 inhibitors in malignancy and chronic disease
Sri N. Batchu;
Sri N. Batchu
1
*Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada M5C 2T2
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Angela S. Brijmohan;
Angela S. Brijmohan
1
*Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada M5C 2T2
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Andrew Advani
*Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada M5C 2T2
Correspondence: Dr Andrew Advani (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 05 2016
Revision Received:
February 29 2016
Accepted:
March 01 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (12): 987–1003.
Article history
Received:
February 05 2016
Revision Received:
February 29 2016
Accepted:
March 01 2016
Citation
Sri N. Batchu, Angela S. Brijmohan, Andrew Advani; The therapeutic hope for HDAC6 inhibitors in malignancy and chronic disease. Clin Sci (Lond) 1 June 2016; 130 (12): 987–1003. doi: https://doi.org/10.1042/CS20160084
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