Dysregulation and restoration of translational homeostasis in fragile X syndrome

• Type of Material: Article
• Authors: Joel D. Richter, University of Massachusetts; Gary Bassell, Emory University; Eric Klann, New York University
• Language: English
• Date: 2015-10-01
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Macmillan Publishers Limited.
• Final Published Version (URL): http://dx.doi.org/10.1038/nrn4001
• Title of Journal or Parent Work: Nature Reviews Neuroscience
• ISSN: 1471-003X
• Volume: 16
• Issue: 10
• Start Page: 595
• End Page: 605
• Grant/Funding Information: This work was supported by Fragile X Syndrome Research Center grant HD082013 from the US National Institutes of Health.
• Keywords: MENTAL-RETARDATION PROTEIN; MESSENGER-RNA TRANSLATION; DEPENDENT TRANSLATION; MOLECULAR-MECHANISMS; GLYCOGEN-SYNTHASE KINASE-3; CYTOPLASMIC POLYADENYLATION; LONG-TERM DEPRESSION; PLURIPOTENT STEM-CELLS; SYNDROME MOUSE MODEL; Neurosciences; Neurosciences & Neurology; Life Sciences & Biomedicine; Science & Technology; FMRP PHOSPHORYLATION; Translation; Autism spectrum disorders; Developmental disorders
• Research Categories: Biology, Genetics; Biology, Neuroscience

Abstract

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.