Autism Spectrum Disorder: Neurexin Proteins

Autism spectrum disorder (ASD) is a group of developmental disabilities characterized by abnormal social interaction, communication, and stereotyped behaviors.
The diagnosis of autism is mainly based on the presence of two major symptoms: social-communication deficits, and restricted and repetitive interests/behaviors.
A 1996 study showed the prevalence of Autism to be 4.5 in 10,000 children. The prevalence increased to 19 in 10,000 American children in 1992 and rose to 1 in 150 in 2002 and 1 in 110 in 2006. The current accepted rate of ASD ∼1% worldwide, placing this disorder as one of the most common developmental disorders in the world.
The mechanisms and pathways going wrong in Autism are extremely complex and still under debate, however, it is interesting to find how some may effect individuals in different ways than others.
One particular area found to be important is the role of neurexin proteins. Neurexins are synaptic adhesion proteins that are known to play a key role in synaptic formation and maintenance. The functional significance is poorly understood, however, mice with a deletion of these proteins show symptoms of ASD. Disruption of a synaptic protein like this would lead to defects in transmission at excitatory and inhibitory synapses, disrupting the E-I balance in post-synaptic neurons which is a key mechanism in ASD.science_figure4
Many mutations in genes encoding neurexins have been associated with ASD. A 2008 study compared symptoms of people with the same chromosomal abnormality with a dysfunctioning neurexin and found the Father didn’t have signs of ASD while the child did showing that the neurexin is not fully causing autism, but must interact with many other factors. However, subtle changes in certain others can contribute to the susceptibility of ASD in others.
There are several different kinds of neurexins (ex. 1α, 2α, 3α, 1β, 2β, 3β). Alpha neurexins are found to be essential for survival. Neurexin-1α is also required for calcium triggered neurotransmitter release and the function of cortical voltage-gated calcium channels. Deletion of α-neurexin genes in mice impaired both excitatory and inhibitory neurotransmitter release, which was attributed to calcium channel disruption, despite normal numbers of cell-surface channels. Despite the reduction in calcium neurotransmitter release and severe impairment in synapse function in α-neurexin knock-out mice, synapse numbers and their ultrastructure are nearly normal, implying that α-neurexins are essential for the proper assembly of synapses into a fully functional unit but not for the initial formation of synapses.
Neurexin proteins are one of possibly thousands of different areas that may be going wrong in the autistic brain and it is important to know the different roles so maybe one day we can find new treatments for this increasingly prevalent problem.
Image citations:
https://www.google.com/search?q=neurexin+proteins&safe=active&espv=2&biw=1215&bih=679&site=webhp&source=lnms&tbm=isch&sa=X&ved=0ahUKEwijnMzWp7rMAhWIWSYKHTMnBEUQ_AUIBigB#imgrc=1wah03MAl3yTqM%3A
https://en.wikipedia.org/wiki/Pervasive_developmental_disorder_not_otherwise_specified
 

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