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Portraying Inhibition of Metabotropic Glutamate Receptor 5 in Fragile X Mice

  • Mihály Hajós
    Correspondence
    Address correspondence to Mihály Hajós, Pharm.D., Ph.D., Laboratory of Translational Neuropharmacology, Section of Comparative Medicine, Yale University School of Medicine, 310 Cedar Street, LSOG, Room 204B, New Haven, CT 06519
    Affiliations
    Laboratory of Translational Neuropharmacology, Section of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut
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      The human genome project and genetic mapping of various common disorders have been considered to have opened a new area in our understanding of the pathophysiology of human illnesses and their treatment. However, the polygenic nature of the vast majority of diseases, interactions between multiple genes and genetic modifiers, as well as epigenetic factors represent a high level of complexity that has turned out to be a real barrier for developing effective therapies on the basis of genetic observations. Monogenic disorders, such as fragile X syndrome (FXS), represent the most promising target for potential drug treatments, given the relatively straightforward cellular/biochemical consequences of the aberrant gene. The article in this issue of Biological Psychiatry by Michalon et al. (
      • Michalon A.
      • Bruns A.
      • Risterucci C.
      • Honer M.
      • Ballard T.M.
      • Ozmen L.
      • et al.
      Chronic metabotropic glutamate receptor 5 inhibition corrects local alterations of brain activity and improves cognitive performance in fragile X mice.
      ) is a direct result of the genetic studies of FXS and subsequent understanding of the physiological role of fragile X mental retardation protein (FMRP), eventually providing a “druggable” target to alleviate this devastating disorder.
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