Autism and the Missing Protein

The autism buzz in the news today arises from the publication in Neuron of a study led by Li-Huei Tsai, PhD, and Picower Professor of Neuroscience at the Massachusetts Institute of Technology (MIT) which suggests that a missing protein may be the key to autism. The brain protein helps synapses develop, the synapses through which neurons convey information, and which are the basis for memory and learning ability development.

As explained by Debbie Halber, Picower Institute for Learning and Memory at MIT, in Missing protein may be key to autism, the study uncovers an enzyme, called Cdk5, that is a key to the activity of the missing protein. Cdk5 is a "kinase", an enzyme that changes proteins, and interacts with a protein called CASK, which is itself important for developing synapses. The absence of Cdk5 can result in the CASK not being present to perform its role:

""Without Cdk5, CASK was not in the right place at the right time, and failed to interact with essential presynaptic components. This, in turn, led to problems with calcium influx." The flow of calcium in and out of neurons affects processes central to nervous system development and plasticity--its ability to change in response to experience. Gene mutations and/or deletions in synaptic cell surface proteins and molecules called neurexins and neuroligins have been associated with autism. The problem with CASK recruitment investigated by the Tsai laboratory creates the same result as these genetic changes."

In comments reported on Reuters, in Missing protein may underlie autism: U.S. study, Tsai was clear about the significance of Cdk5 failing to facilitate CASK in the development of autism:

""We show that if Cdk5 fails to facilitate CASK, then there is a very profound defect in synapse formation, ....

The most accepted hypothesis for autism is that there is a defect in synapse formation," Tsai said, adding that mutations of genes directly connected to CASK have already been identified as being associated with autism.

Mutations of CASK and Cdk5 are also identified in certain patients with mental retardation.

"I think this study strongly suggests this pathway involving Cdk5 ... is intimately involved (in autism)," she said.