title: The mGluR theory of fragile X mental retardation.
abstract: Many of the diverse functional consequences of activating group 1 metabotropic glutamate receptors require translation of pre-existing mRNA near synapses. One of these consequences is long-term depression (LTD) of transmission at hippocampal synapses. Loss of fragile X mental retardation protein (FMRP), the defect responsible for fragile X syndrome in humans, increases LTD in mouse hippocampus. This finding is consistent with the growing evidence that FMRP normally functions as a repressor of translation of specific mRNAs. Here we present a theory that can account for diverse neurological and psychiatric aspects of fragile X syndrome, based on the assumption that many of the protein-synthesis-dependent functions of metabotropic receptors are exaggerated in fragile X syndrome. The theory suggests new directions for basic research as well as novel therapeutic approaches for the treatment of humans with fragile X, the most frequent inherited cause of mental retardation and an identified cause of autism.
authors.affiliation: The Picower Center for Learning and Memory, Howard Hughes Medical Institute and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. mbear@mit.edu
authors.forename: Mark F
authors.initials: MF
authors.lastname: Bear
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Huber
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Warren
mesh_terms: D000818:Animals; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000503:physiopathology*; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D016601:RNA-Binding Proteins; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D018094:Receptors, Metabotropic Glutamate; C497683:FMR1 protein, human