Wey HY, Gilbert TM, Zürcher NR, She A, Bhanot A, Taillon BD, Schroeder FA, Wang C, Haggarty SJ, Hooker JM. Insights into neuroepigenetics through human histone deacetylase PET imaging. Sci Transl Med. 2016 Aug 10;8(351):351ra106. PubMed.

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  1. The paper by Wey et al. on PET imaging of HDACs appears to provide an important new proof of principle, showing that key epigenetic regulators can be imaged in human brain. There is growing evidence that class I HDACs play important roles in a highly diverse range of brain functions, including, as shown primarily by Tsai and colleagues, learning and memory. Class I HDACs are also increasingly suspected to be significant players in Alzheimer’s disease and other major disorders.

    However, in part because of their pleiotropic functions and ubiquitous involvement in chromatin modulation, studies of specific targets and actions of HDACs have been hindered. Most research to date has used drugs or genetic manipulations, the effects of which can be difficult to interpret in a region-, cell-, or gene-specific manner. Therefore, there is a clear need for technological advances that will enable more specific analyses of the targets and mechanisms of these key epigenetic regulators.

    The development of this new selective HDAC ligand for PET imaging appears to be an important step in this direction that could seemingly support analyses of concurrent HDAC expression in multiple brain regions during cognitive activity or in disease. Clearly, the availability of this ligand for use in humans has the important advantage of not having to rely on animal models that may not fully model a human disease or function. Nonetheless, it seems likely that a substantial amount of additional work in animals will be required to assess how well the ligand informs about HDAC function during dynamic interventions and pathological conditions.

    View all comments by Philip Landfield

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