@article{d73b5bef36174fdfb5c42f38c2f0cb33,
title = "A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders",
abstract = "Altered synaptic structure and function is a major hallmark of fragile X syndrome (FXS), autism spectrum disorders (ASDs), and other intellectual disabilities (IDs), which are therefore classified as synaptopathies. FXS and ASDs, while clinically and genetically distinct, share significant comorbidity, suggesting that there may be a common molecular and/or cellular basis, presumably at the synapse. In this article, we review brain architecture and synaptic pathways that are dysregulated in FXS and ASDs, including spine architecture, signaling in synaptic plasticity, local protein synthesis, (m)RNA modifications, and degradation. mRNA repression is a powerful mechanism for the regulation of synaptic structure and efficacy. We infer that there is no single pathway that explains most of the etiology and discuss new findings and the implications for future work directed at improving our understanding of the pathogenesis of FXS and related ASDs and the design of therapeutic strategies to ameliorate these disorders. ASDs and comorbid diseases such as FXS are caused by altered synaptic structure and connectivity. Bagni and Zukin review the construction and elimination of synapses: mild alterations in these pathways affect the equilibrium during development and cause the disease.",
keywords = "ASDs, ERK, FMRP, FXS, MNK, TSC, mGluRs, mRNA metabolism, mTOR, synaptopathies",
author = "Claudia Bagni and Zukin, {R. Suzanne}",
note = "Funding Information: The authors are extremely thankful to Vittoria Mariano and Adrian Lo for their help in preparing the figures and Michael Bennet, Tilmann Achsel, Eleonora Rosina, Nuria Dom{\'i}nguez Iturza, and Alexandros Kanellopoulos for critically reading the manuscript and discussions. This work was supported by SNSF 310030-182651 and NCCR Synapsy 51NF40-158776 (Switzerland), Novartis (Switzerland), Italian Fragile X Association (Italy) KU Leuven OTR (Belgium), Telethon Italy (GGP15257) and Department of Defense WW81XWH-15-1-0361 (USA) = to C.B., National Institutes of Health grant MH-092877, a grant from the Simons Foundation and a FRAXA fellowship (USA) to R.S.Z. Funding Information: The authors are extremely thankful to Vittoria Mariano and Adrian Lo for their help in preparing the figures and Michael Bennet, Tilmann Achsel, Eleonora Rosina, Nuria Dom{\'i}nguez Iturza, and Alexandros Kanellopoulos for critically reading the manuscript and discussions. This work was supported by SNSF 310030-182651 and NCCR Synapsy 51NF40-158776 (Switzerland), Novartis (Switzerland), Italian Fragile X Association (Italy) KU Leuven OTR (Belgium), Telethon Italy ( GGP15257 ) and Department of Defense WW81XWH-15-1-0361 (USA) = to C.B., National Institutes of Health grant MH-092877 , a grant from the Simons Foundation and a FRAXA fellowship (USA) to R.S.Z. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = mar,
day = "20",
doi = "10.1016/j.neuron.2019.02.041",
language = "English (US)",
volume = "101",
pages = "1070--1088",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",
}