Fragile X Syndrome: from molecular pathology to therapy.
Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability due to the silencing of the FMR1 gene encoding FMRP (Fragile X Mental Retardation Protein), an RNA-binding protein involved in different steps of RNA metabolism. Of particular interest is the key role of FMRP in translational regulation. Since the first functional characterizations of FMRP, its role has been underlined by its association with actively translating polyribosomes. Furthermore, a plethora of mRNA targets of FMRP have been identified. In the absence of FMRP the deregulation of translation/transport/stability of these mRNAs has a cascade effect on many pathways, resulting into the final phenotype. We review here a set of targets of FMRP (mRNAs and proteins) that may have an impact on the FXS phenotype by deregulating some key cellular processes, such as translation, cytoskeleton remodeling and oxidative stress. The manipulation of these abnormal pathways by specific drugs may represent new therapeutic opportunities for FXS patients.
Institute of Molecular and Cellular Pharmacology, CNRS UMR7275, University of Nice Sophia Antipolis, Route des Lucioles, 06560 Valbonne, France.
Thomas
T
Maurin
Institute of Molecular and Cellular Pharmacology, CNRS UMR7275, University of Nice Sophia Antipolis, Route des Lucioles, 06560 Valbonne, France.
Samantha
S
Zongaro
Institute of Molecular and Cellular Pharmacology, CNRS UMR7275, University of Nice Sophia Antipolis, Route des Lucioles, 06560 Valbonne, France. Electronic address: bardoni@ipmc.cnrs.fr.
Barbara
B
Bardoni
D003599:Cytoskeleton / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D008957:Models, Genetic; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress / Q000235:genetics
D051860:Fragile X Messenger Ribonucleoprotein 1; D035683:MicroRNAs
Actin cytoskeleton dynamics; Oxidative stress; RNA-binding protein; Translational regulation; microRNA