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Cited by 48Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchDown syndrome and intellectual disability research

Molecular and Cellular Aspects of Mental Retardation in the Fragile X Syndrome: From Gene Mutation/s to Spine Dysmorphogenesis

De Rubeis, Silvia, Fernández, Esperanza, Buzzi, Andrea, Di Marino, Daniele, Bagni, Claudia·2012·Advances in Experimental Medicine and Biology
DOI 10.1007/978-3-7091-0932-8_23
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Abstract

The Fragile X syndrome (FXS) is the most frequent form of inherited mental retardation and also considered a monogenic cause of Autism Spectrum Disorder. FXS symptoms include neurodevelopmental delay, anxiety, hyperactivity, and autistic-like behavior. The disease is due to mutations or loss of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein abundant in the brain and gonads, the two organs mainly affected in FXS patients. FMRP has multiple functions in RNA metabolism, including mRNA decay, dendritic targeting of mRNAs, and protein synthesis. In neurons lacking FMRP, a wide array of mRNAs encoding proteins involved in synaptic structure and function are altered. As a result of this complex dysregulation, in the absence of FMRP, spine morphology and functioning is impaired. Consistently, model organisms for the study of the syndrome recapitulate the phenotype observed in FXS patients, such as dendritic spine anomalies and defects in learning. Here, we review the fundamentals of genetic and clinical aspects of FXS, devoting a specific attention to ASD comorbidity and FXS-related diseases. We also review the current knowledge on FMRP functions through structural, molecular, and cellular findings. Finally, we discuss the neuroanatomical, electrophysiological, and behavioral defects caused by FMRP loss, as well as the current treatments able to partially revert some of the FXS abnormalities.

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Crossref · 10.1007/978-3-7091-0932-8_23

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  • FMRP forms large cytoplasmic ribonucleoparticles containing other proteins and RNAs.

    “FMRP forms large cytoplasmic ribonucleoparticles containing several other proteins (61) and RNAs (62,63).”

    From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [62]

  • High-throughput screenings and accompanying small-scale studies show that many neuronal mRNAs, especially those encoding presynaptic and postsynaptic proteins, are deregulated in the absence of FMRP, suggesting that concerted alteration of many proteins contributes to the fragile X syndrome phenotype.

    “High-throughput screenings supported by accompanying small scale studies have revealed that a wide array of neuronal mRNAs, with a large proportion encoding for presynaptic and postsynaptic proteins, is deregulated in the absence of FMRP, suggesting that concerted alteration of many proteins contributes to the FXS phenotype (62).”

    From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [62]

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Authors
De Rubeis, S., Fernández, E., Buzzi, A., Di Marino, D., & Bagni, C.
Affiliations
  • Vlaams Instituut voor Biotechnologie (BE)
  • University of Rome Tor Vergata (IT)
Corresponding author
Bagni, Claudia
ORCID
Venue
Advances in Experimental Medicine and Biology
Publisher
Springer Vienna
Published
2012
Volume
970
Pages
517-551
ISSN
0065-2598 (ISSN-L)
DOI
10.1007/978-3-7091-0932-8_23
OpenAlex
W2245762304
Cited by
48
References
230
Citations by year
2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 7 · 2013: 15 · 2012: 8
FWCI
24.39
Type
book chapter
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Advances in experimental medicine and biology (publishedVersion)
  • PubMed (publishedVersion)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
  • Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
  • Lirias (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
Keywords
fragile X syndrome, FMRP, intellectual disability, autism spectrum disorder, RNA-binding proteins, mRNA degradation, synaptic dysfunction, learning deficits
MeSH terms
Animals, Brain, Child, Dendrites, Disease Models, Animal, Drosophila melanogaster, Fragile X Syndrome, Gonads, Humans, Male, Mutation, Phenotype, RNA, Messenger, Protein Biosynthesis, Zebrafish, Gene Expression, RNA Stability, Mice, Fragile X Messenger Ribonucleoprotein 1, Molecular Targeted Therapy

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