advancing research in basic sciences and mathematics
Autism and autism spectrum disorders are common developmental disorders in children for which there is currently no cure. Several hallmarks of autism include difficulties engaging in social interactions, communicating with others, and repeating movements or having limited interests. It is thought that while environmental and genetic factors may be associated with autism, there may also be abnormalities in how different types of neurons in the brain connect with each other during development. During this dynamic developmental period, one type of neurons, the excitatory pyramidal neurons, may not connect properly at the synapse with another type of neuron known as inhibitory interneurons. A pronounced shift in the homeostasis at the synapse, where the two neurons receive and transmit information via neurotransmitters, may play an important but unexamined role in disrupting the normal cognitive abilities of the developing brain that lead to characteristic clinical features of autism.
Of particular relevance and interest to autism research is the molecule cyclin-dependent kinase 5 (Cdk5), a serine/threonine protein kinase that is crucial for normal brain development and patterning in mouse models. Cdk5 is present at the synapse and may play a key role in recruiting molecules necessary for proper synapse formation by phosphorylating them. A working model suggests that Cdk5 may affect synapse stabilization through a key structure, the dendritic spine, which receives neurotransmitters and modulates rapid electrical activity changes in the brain. Disrupting Cdk5 in mouse models will shed new insight into how Cdk5 contributes to synapse stabilization and maintains normal neurotransmission. By using various mouse models to understand how the loss of Cdk5 in both excitatory neurons and inhibitory interneurons affects dendritic spines at the synapse, targeting key proteins phosphorylated by Cdk5 at the synapse can be one of many potentially novel therapeutic approaches for autism and autism spectrum disorders.
Copyright 2008 © Simons Foundation