Research ArticleBrain Imaging

Insights into neuroepigenetics through human histone deacetylase PET imaging

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Science Translational Medicine  10 Aug 2016:
Vol. 8, Issue 351, pp. 351ra106
DOI: 10.1126/scitranslmed.aaf7551

Brain epigenetics revealed

Certain enzymes called histone deacetylases, or HDACs, are part of the epigenetic machinery that regulates gene transcription. In neurological disorders, HDACs change expression in regions throughout the brain, but their dynamic contribution to human disease development over time is unknown. Wey et al. therefore developed and applied an HDAC imaging probe, called Martinostat, to visualize HDAC expression in the living brain. Martinostat was previously tested in rodents and nonhuman primates, and here, it is used for the first time in humans. The authors saw surprisingly conserved regions of HDAC expression in the healthy brain, suggesting tightly regulated epigenetic processes. In human stem cell–derived neural progenitor cells, Martinostat engaged the subset HDACs that regulate downstream genes important for neuroplasticity, memory, and neurodegeneration, supporting its use in monitoring and understanding brain pathologies like Alzheimer’s disease.

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