Fig. 1

Synaptic translation and signaling pathways modulated by FMRP (a) and dysregulation of these pathways in the absence or significant reduction of FMRP (b). Shaded areas in (b) indicate groups of targets for different strategies aimed at treatment of FXS by correcting dysregulated neuronal pathways. Shaded areas are numbered according to type of treatment strategy and correspond to numbering system for treatment strategies in the text as follows: (1) reduction of activity in pathways that transduce signals from group 1 mGluRs or other Gq-linked receptors to the dendritic translational machinery via (1a) extracellular pathway (receptor) blockers and/or (1b) intracellular pathway blockers; (2) reduction of activity of individual proteins regulated by FMRP; (3) increasing surface AMPA receptors and/or activity; (4) modification of activity of other receptors/proteins that regulate synaptic activity; and (5) blocking translation of mRNAs regulated by FMRP using antisense technology