Dysregulation and restoration of translational homeostasis in fragile X syndrome.
Fragile X syndrome (FXS), the most-frequently inherited form of intellectual disability and the most-prevalent single-gene cause of autism, results from a lack of fragile X mental retardation protein (FMRP), an RNA-binding protein that acts, in most cases, to repress translation. Multiple pharmacological and genetic manipulations that target receptors, scaffolding proteins, kinases and translational control proteins can rescue neuronal morphology, synaptic function and behavioural phenotypes in FXS model mice, presumably by reducing excessive neuronal translation to normal levels. Such rescue strategies might also be explored in the future to identify the mRNAs that are critical for FXS pathophysiology.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01545, USA.
Joel D
JD
Richter
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Gary J
GJ
Bassell
Center for Neural Science, New York University, New York City, New York 10003, USA.
Eric
E
Klann
D000818:Animals; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000096:biosynthesis / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000503:physiopathology; D015870:Gene Expression; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger