Neural circuit molecules implicated in Autism-spectrum disorders
Over the past decade, there has been growing evidence that the strength of these synaptic interactions (also known as synaptic plasticity) are dynamic. Moreover, it turns out that the plasticity of these connections is critical for neuronal development and cognitive functions of the brain. I had the opportunity to hear Nobel laureate Dr. Sudhof, at this year’s Society of Neuroscience conference, speak about their research highlighting the importance of synaptic proteins with neurological disorders such as Autism and Schizophrenia. In 1992, Dr. Sudhof’s group in the quest to identify the membrane receptor of alpha-latrotoxin (the toxin from Black-widow spider venom), first cloned Neurexin. Further work by Dr. Sudhof and others has proven that most of the neuronal synaptic plasticity is mediated by intersynaptic proteins such as neurexins.
Source: http://www.bradleymonk.com/wiki
A number of synaptic proteins such as cerebellin, neurolignin, LRRTM2 and latrophillin bind and activate neurexin. But it was discovered that both alpha and beta neurexins are highly polymorphic due to extensive alternative splicing. Interestingly, these polymorphisms are highly regulated and show cell-type selective splicing and also change ligand binding characteristics.
Over fifty different neuroligin gene mutations have been identified to be related to autism. But, the genetic background of individuals and not individual mutations is what determines physical signs and symptoms in patients. But sadly we are still a long way away from truly understanding this phenomenon. Sudhof himself said the following (I’m paraphrasing him here) regarding the increasing frustration in lack of progress in neuroscience among general public -
Autism research field hasn't failed, we have only failed to communicate the magnitude of the challenge.
Progress in cancer research has required >$1 trillion, it should not surprise us if understanding brain disorders would take at least as much or even more?
Here is further reading, if you are interested about synaptic plasticity and autism -
Synaptic proteins and receptors defects in autism spectrum disorders
Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors.