Potential therapeutic interventions for fragile X syndrome.
Fragile X syndrome (FXS) is caused by a lack of the fragile X mental retardation protein (FMRP); FMRP deficiency in neurons of patients with FXS causes intellectual disability (IQ<70) and several behavioural problems, including hyperactivity and autistic-like features. In the brain, no gross morphological malformations have been found, although subtle spine abnormalities have been reported. FXS has been linked to altered group I metabotropic glutamate receptor (mGluR)-dependent and independent forms of synaptic plasticity. Here, we discuss potential targeted therapeutic strategies developed to specifically correct disturbances in the excitatory mGluR and the inhibitory gamma-aminobutyric (GABA) receptor pathways that have been tested in animal models and/or in clinical trials with patients with FXS.
Levenga
Josien
J
CBG-Department of Clinical Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
de Vrij
Femke M S
FM
Oostra
Ben A
BA
Willemsen
Rob
R
D000818:Animals; D001569:Benzodiazepines / Q000627:therapeutic use; D018690:Excitatory Amino Acid Agonists / Q000627:therapeutic use; D005600:Fragile X Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D064529:Receptor, Metabotropic Glutamate 5; D018079:Receptors, GABA / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D018690:Excitatory Amino Acid Agonists; D064529:Receptor, Metabotropic Glutamate 5; D018079:Receptors, GABA; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D001569:Benzodiazepines