Translational endpoints in fragile X syndrome.
Neurosci Biobehav Rev
; 46 Pt 2: 256-69, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24184744
ABSTRACT
Fragile X syndrome (FXS) occurs in less than 10% of the intellectually disabled (ID) population. The cause of FXS is a CGG trinucleotide repeat longer than 200 CGG units within the first exon of the FMR1 gene, which leads to hypermethylation and consequently silencing of the FMR1 gene. The lack of FMR1's gene product, the fragile X mental retardation protein (FMRP) in neurons is the cause of the ID in patients with FXS. FMRP plays an important role in local protein synthesis at the synapse including modulation of synaptic plasticity. The advancing knowledge about the cellular function of FMRP has led to the identification of translational endpoints for future therapeutic intervention strategies. This review highlights the challenging routes to the identification of reliable outcome measures in preclinical studies using both cellular models and Fmr1 knockout mice. Finally, clinical studies carried out to correct intellectual and behavioral deficits in patients with FXS, using a variety of existing and new drugs, are discussed.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína do X Frágil da Deficiência Intelectual
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Terapia de Alvo Molecular
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Síndrome do Cromossomo X Frágil
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Plasticidade Neuronal
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article