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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1070-1088 |
| Number of pages | 19 |
| Journal | Neuron |
| Volume | 101 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 20 2019 |
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Keywords
- ASDs
- ERK
- FMRP
- FXS
- mGluRs
- MNK
- mRNA metabolism
- mTOR
- synaptopathies
- TSC
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders. / Bagni, Claudia; Zukin, R. Suzanne.
In: Neuron, Vol. 101, No. 6, 20.03.2019, p. 1070-1088.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders
AU - Bagni, Claudia
AU - Zukin, R. Suzanne
PY - 2019/3/20
Y1 - 2019/3/20
N2 - 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.
AB - 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.
KW - ASDs
KW - ERK
KW - FMRP
KW - FXS
KW - mGluRs
KW - MNK
KW - mRNA metabolism
KW - mTOR
KW - synaptopathies
KW - TSC
UR - http://www.scopus.com/inward/record.url?scp=85062458853&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062458853&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2019.02.041
DO - 10.1016/j.neuron.2019.02.041
M3 - Review article
VL - 101
SP - 1070
EP - 1088
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 6
ER -