A number of specific gene mutations are associated with intellectual disability and autism, providing hope that understanding common downstream effects might shed light on the pathophysiology of autism spectrum disorders. Bear and colleagues now show that mutations in fragile X mental retardation 1 (FMR1) and tuberous sclerosis 2 (TSC2), which are associated with similar behavioural impairments, have opposing effects on metabotropic glutamate receptor 5 (mGluR5) function and synaptic protein synthesis. In fragile X syndrome (FXS), silencing of FMR1 increases mRNA translation downstream of mGluR5 activation, leading to increased long-term depression (LTD) at mGluR5-expressing synapses. The mutations in TSC1 or TSC2 that cause tuberous sclerosis are also thought to influence mRNA translation and synaptic function, suggesting that similar mechanisms might be involved.
展开▼
