Science Translational Medicine: New Protein Pathways Link Autism and Related Disorders

A new molecular map reveals protein “social networks” in the brain that could potentially be targeted by drugs to treat several different forms of autism, according to a new study in Science Translational Medicine.

The findings in the 8 June issue of the journal describe how proteins associated with autism interact with hundreds of other proteins, and may serve as a platform for discovering new genes related to autism disorders.

“We hope that the network will help in the design of future therapies,” said co-author Huda Zogbhi, physician and medical researcher at Baylor College of Medicine. “To date, there are tens of autism-causing genes and it is anticipated that there will be hundreds.”

Classic autism is characterized by three cardinal features: Loss of language and communication, impaired social behavior, and repetitive movements. In neurological disorders like Fragile X and Angelman syndrome, which fall under the category of syndromic autism, these characteristics are part of a much larger set of symptoms.

Syndromic autism can often be traced back to a single gene, but researchers have had difficulty pinpointing the genetic basis of classic autism. Aiming to find common molecular pathways that underpin both classic and syndromic autism, Zogbhi and colleagues mapped thousands of protein-protein interactions, using a library of human protein-coding DNA sequences.

Using known autism-associated proteins as bait, the researchers went fishing in the DNA library to attract partner proteins, and found about 500 proteins that interacted with the autism-associated proteins.

The researchers showed that all of the proteins linked to autism individually are all connected in some way by sharing partner proteins. The team’s protein interaction map also highlights very tightly connected proteins, such as those known to be mutated in Fragile X syndrome.

Their map also shows that two proteins associated with classic autism (SHANK3 and TSC1), interact with each other and share 21 common protein partners. The results show that these protein interactions form well-worn pathways in the brains of individuals with autism, and that these pathways are closely related to the protein interactions involved in disorders such as Fragile X syndrome, Angelman syndrome, and Rett syndrome.

“Studying these and developing therapies for one genetic disorder at a time will be challenging and slow,” Zoghbi said, “but using protein interaction networks to study a group of autism disorders whose proteins closely interact might prove more efficient for identifying pathways amenable to therapeutic manipulation in that group.”

Nadia Ramlagan

8 June 2011