Table 1.
Manipulations that reset translational homeostasis and rescue phenotypes in FXS mice
| Target | Rescue strategy | Normalization of excessive protein synthesis? | Normalization of mGluR-induced LTD? | Behavioural phenotypes normalized | Refs |
|---|---|---|---|---|---|
| mGluR5 | Genetic reduction and mGluR5 antagonist | Yes | Yes | Extinction memory, startle response, locomotor activity and audiogenic seizures | 6,76 |
| GABAB receptor | receptor GABAB antagonist | Yes | ND | Audiogenic seizures, repetitive behaviour, locomotor activity and motor learning | 80 |
| PIKE | Genetic reduction | Yes | Yes | Repetitive behaviours and nest building | 18 |
| p110β subunit of PI3K | Genetic reduction | Yes | ND | Goal-directed decision making, behavioural flexibility, nest building and repetitive behaviour | 19 |
| HOMER1A | Genetic reduction | Yes | No | Audiogenic seizures and anxiety behaviour | 17 |
| TSC2 | Genetic reduction | Yes | Yes | Context discrimination | 14 |
| S6K1 | Genetic reduction | Yes | Yes | Recognition memory, behavioural flexibility, social novelty and motor learning | 15 |
| CPEB | Genetic reduction | Yes | Yes | Audiogenic seizures, anxiety behaviour, nest building and spontaneous alteration | 8 |
| RAS | Farnesyltransferase inhibitor | Yes | Yes | Audiogenic seizures | 88 |
| MEK1 | MEK1 inhibitor | Yes | ND | Audiogenic seizures | 77 |
| MNK1, MNK2 and p-eIF4E | Genetic reduction of MNK1 and/or MNK2, MNK inhibitor, and genetic reduction of p-eIF4E | Yes | Yes | Social novelty, social interaction, anxiety behaviour and audiogenic seizures | 16 |
| MMP9 | Genetic reduction and MMP9 inhibitor | ND | Yes | Anxiety behaviour, locomotor activity and social novelty | 20 |
| CB1R | Genetic reduction and CB1R antagonist | ND | ND | Recognition memory, anxiety behaviour, nociception and audiogenic seizures | 21 |
CB1R, cannabinoid 1 receptor; CPEB, cytoplasmic polyadenylation element binding protein; FXS, fragile X syndrome; LTD, long term depression; MEK1, MAPK/ERK kinase 1; mGluR, metabotropic glutamate receptor; MMP9, matrix metalloproteinase 9; MNK, MAP kinase-interacting serine/threonine-protein kinase; ND, not determined; PI3K, phosphoinositide 3-kinase; p-eIF4E, phosphorylated eukaryotic initiation factor 4E; PIKE, PI3K enhancer; S6K1, p70 S6 kinase 1; TSC2, tuberous sclerosis complex 2.