Table of Contents

Reviews

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  • Gerard B. Fox,
  • Chih-Liang Chin,
  • Feng Luo,
  • Mark Day,
  • and Bryan F. Cox

  Translational NeuroImaging of the CNS: Novel Pathways to Drug Development

  Mol Interv December 2009 9:302-313; doi:10.1124/mi.9.6.6
  • Abstract
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  Recent advances in high-resolution and high-sensitivity equipment, along with the development of selective biological probes and biomarkers, are rapidly providing new opportunities to investigate drug efficacy and safety. Depending on the modality used, imaging has applications throughout the entire drug lifecycle, and can provide data for target validation, defining mechanism of action, demonstrating efficacy/safety in both preclinical and clinical settings, and applying biomarkers of biological activity. Information gained in these regards can have direct bearing upon the investment of time and resources for phase 2 trials. Imaging studies allow longitudinal measures in the same subject, and recent developments in small-animal scanners can provide translational data for transition from preclinical into early clinical studies. A new wave of neuroimaging studies that engender useful biomarkers of disease for translational research promise to revolutionize the development of therapeutics for a range of neurological diseases.

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  • Catherine A. Musselman and
  • Tatiana G. Kutateladze

  PHD Fingers: Epigenetic Effectors and Potential Drug Targets

  Mol Interv December 2009 9:314-323; doi:10.1124/mi.9.6.7
  • Abstract
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  We all know the string of usual suspects: A, T, G, and C. And we’ve known, for some time, that their intimate association with the histones goes much deeper than a mere packaging story: these basic proteins appear to undergo posttranslational modifications that regulate gene activity. Investigators are coming ever closer to understanding exactly how these modifications are being “read” by proteins that—in the case presented here—possess certain zinc fingers (aka PHD fingers). We can now be certain that modifications of specific residues on distinct histones interact with PHD fingers of proteins that in turn recruit additional protein associates to chromatin. The observed complexes can result in specific gene activation or silencing, depending on how the PHD finger–containing proteins “read” the posttranslational cues that reside on histones. In certain instances, mutational alteration of PHD finger–containing proteins has been related to disease; whether new therapeutics can be devised to counter such malfeasance is under ongoing investigation.