Summary A link between protein synthesis and Autism Spectrum Disorders (ASD) has been identified.
Regulation of protein synthesis, also termed mRNA translation, is the process by which cells manufacture proteins. This mechanism is involved in all aspects of cell and organism function.
A new study in mice by researchers from McGill University and the University of Montreal has found that abnormally high synthesis of a group of neuronal proteins called neuroligins results in symptoms similar to those diagnosed in ASD.
The study also revealed that autism-like behaviours could be rectified in adult mice with compounds inhibiting protein synthesis, or with gene-therapy targeting neuroligins.
Autism spectrum disorders (ASD) encompass a wide array of neurodevelopmental diseases that affect three areas of behaviour: social interactions, communication and repetitive interests or behaviours. According to the U.S.-based Centers for Disease Control and Prevention, 1 in 88 children suffer from ASD, and the disorder is reported to occur in all racial, ethnic, and socio-economic groups. ASDs are almost five times more common among boys (1 in 54) than among girls (1 in 252).
“My lab is dedicated to elucidating the role of dysregulated protein synthesis in cancer etiology. However, our team was surprised to discover that similar mechanisms may be implicated in the development of ASD”, explained Prof. Nahum Sonenberg, from McGill’s Dept. of Biochemistry, Faculty of Medicine, and the Goodman Cancer Research Centre.
“We used a mouse model in which a key gene controlling initiation of protein synthesis was deleted. In these mice, production of neuroligins was increased. Neuroligins are important for the formation and regulation of connections known as synapses between neuronal cells in the brain and essential for the maintenance of the balance in the transmission of information from neuron to neuron,” Prof. Sonenberg said.
Christos Gkogkas, a postdoctoral fellow at McGill and lead author, added “Since the discovery of neuroligin mutations in individuals with ASD in 2003, the precise molecular mechanisms implicated remain unknown.”
The researchers were also able to reverse changes in inhibition and augment autistic behaviours by manipulating a second neuroligin.
