Fragile X syndrome: From protein function to therapy.

Details

Serval ID
serval:BIB_1DAB98D05046
Type
Article: article from journal or magazin.
Collection
Publications
Title
Fragile X syndrome: From protein function to therapy.
Journal
American journal of medical genetics. Part A
Author(s)
Bagni C., Oostra B.A.
ISSN
1552-4833 (Electronic)
ISSN-L
1552-4825
Publication state
Published
Issued date
11/2013
Volume
161A
Number
11
Pages
2809-2821
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Abstract
Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and autism. The FMR1 gene contains a CGG repeat present in the 5'-untranslated region which can be unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In patients with fragile X syndrome (FXS), a repeat length exceeding 200 CGGs generally leads to methylation of the repeat and the promoter region, which is accompanied by silencing of the FMR1 gene. The disease is a result of lack of expression of the fragile X mental retardation protein leading to severe symptoms, including intellectual disability, hyperactivity, and autistic-like behavior. The FMR1 protein (FMRP) has a number of functions. The translational dysregulation of a subset of mRNAs targeted by FMRP is probably the major contribution to FXS. FMRP is also involved in mRNA transport to synapses where protein synthesis occurs. For some FMRP-bound mRNAs, FMRP is a direct modulator of mRNA stability either by sustaining or preventing mRNA decay. Increased knowledge about the role of FMRP has led to the identification of potential treatments for fragile X syndrome that were often tested first in the different animal models. This review gives an overview about the present knowledge of the function of FMRP and the therapeutic strategies in mouse and man.

Keywords
Animals, Disease Models, Animal, Fragile X Mental Retardation Protein/chemistry, Fragile X Mental Retardation Protein/genetics, Fragile X Mental Retardation Protein/metabolism, Fragile X Syndrome/drug therapy, Fragile X Syndrome/genetics, Fragile X Syndrome/metabolism, GABA Agonists/pharmacology, GABA Agonists/therapeutic use, Gene Expression Regulation, Humans, Molecular Targeted Therapy, Receptors, Metabotropic Glutamate/antagonists & inhibitors, Receptors, Metabotropic Glutamate/metabolism, Signal Transduction
Pubmed
Open Access
Yes
Create date
06/03/2017 18:23
Last modification date
20/08/2019 13:54
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