Quantitative proteomic approach to understanding and treating autism

Autism spectrum disorders are a clinically heterogeneous group of disorders that share common features. Only an estimated 10 to 15 percent of autism cases are monogenic — caused by mutations in a single gene — but the molecular alterations in these disorders could reveal common pathogenic mechanisms shared across the spectrum.

Many of the mutations linked to autism in humans lead to disrupted activity of synapses — the junctions between neurons — and altered synthesis of synaptic proteins. Peng Jin and Junmin Peng at Emory University in Atlanta, Georgia, have developed a high-throughput proteomic analysis using metabolically labeled mice. The mice eat food that contains labeled amino acids, showing newly synthesized proteins. With SFARI funding, they used this method to compare alterations in synaptic protein synthesis in various mouse models of autism-linked monogenic disorders to test whether the abnormal neuronal activity among these mouse models is due to altered synaptic protein synthesis.

Intriguingly, they found very few proteins with consistent alterations among the mice, suggesting that factors other than synaptic protein synthesis must contribute to the overall phenotypes associated with autism.