title: The pathophysiology of fragile X (and what it teaches us about synapses).
abstract: Fragile X is the most common known inherited cause of intellectual disability and autism, and it typically results from transcriptional silencing of FMR1 and loss of the encoded protein, FMRP (fragile X mental retardation protein). FMRP is an mRNA-binding protein that functions at many synapses to inhibit local translation stimulated by metabotropic glutamate receptors (mGluRs) 1 and 5. Recent studies on the biology of FMRP and the signaling pathways downstream of mGluR1/5 have yielded deeper insight into how synaptic protein synthesis and plasticity are regulated by experience. This new knowledge has also suggested ways that altered signaling and synaptic function can be corrected in fragile X, and human clinical trials based on this information are under way.
authors.affiliation: Howard Hughes Medical Institute, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. abhakar@mit.edu
authors.forename: Asha L
authors.initials: AL
authors.lastname: Bhakar
authors.forename: Gül
authors.initials: G
authors.lastname: Dölen
authors.forename: Mark F
authors.initials: MF
authors.lastname: Bear
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000502:physiology*; D005600:Fragile X Syndrome / Q000378:metabolism / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009473:Neuronal Plasticity / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology; D012313:RNA / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012313:RNA; D018094:Receptors, Metabotropic Glutamate; C497683:FMR1 protein, human; C104077:metabotropic glutamate receptor type 1