AUTISM

Up to one-third of autism cases could be

caused by a single protein deficit
Increased brain levels of the nSR100 protein may be sufficient to improve the abnormal
behaviors typical of autism
A third of cases of autism could be explained by the deficit nSR100 in the brain -

Up to one-third of autism cases could be the consequence of a deficit in the levels of a

protein in the brain. This is shown by a study conducted by researchers at the University
of Toronto (Canada) and in which participated the Centre for Genomic Regulation in
Barcelona, where it is observed that the lack of the nSR100v protein -also known as
'SRRM4' is enough to explain some of the typical signs of autism, in case of problems
in social interactions. In fact, new research suggests that raising the concentration of this
protein in the brain may help correct some of the characteristic signs and symptoms of
autism spectrum disorders (ASDs).
As Sabine Cordes, co-director of this research published in the journal Molecular Cell,
explains "in a previous work we had already found an association between levels of the
protein nSR100 and autism. But now we have seen that reduced levels of this protein
may actually be the cause of the disorder. In fact, with a decrease of only 50% in
nSR100 levels the characteristic signs of autistic behavior are observed.
The nSR100 protein is a key regulator in alternative splicing that takes place in the
brain. And exactly, what is this 'splicing' or alternative splice? Its a process which
makes possible the production of multiple proteins with different functions from the
same gene. Basically, a gene - that is, a specific sequence of DNA - encodes an RNA
from which a protein is produced. However, the 'raw' sequence of this RNA can be
manipulated to give rise to different proteins. Thus, this RNA can be 'chopped' and
'glued' or 'spliced'. Logically, through this 'alternative splicing' an almost unlimited
supply of proteins are possible from a number of not-so-unlimited genes.
In this context, the authors had already shown in a previous study that the brains of
people with autism have a deficient levels of protein nSR100. So researchers have
already raised the point that autism could be caused, at least partially, by an
accumulation of incorrectly 'spliced' proteins in brain cells. But is this deficiency a
simple consequence of autism or, on the contrary, can it actually be the cause of the
development of this disorder?
To answer this question, the authors used mice that were manipulated genetically and
what they saw is that the reduction by half of the normal levels of nSR100 was
enough for some of the characteristic signs and symptoms of autism to appear, in
case of avoidance of social interactions and a very significant increase in sensitivity to
noise.
Moreover, animals with an absence or deficiency of the nSR100 protein also showed
some of the typical characteristics of autism in humans, in the case of alterations in
brain connections and in the 'alternative splicing' of proteins. And what is more
important, the authors also found that levels of nSR100 are directly associated with
neuronal activity.
According to Mathieu Quesnel-Vallieres, co-author of the research, "if you have an
increase in neuronal activity, which happens in many types of autism, then there is an
interruption of the 'alternative splicing' program which produces the typical behaviors of
the disorder. "

Correct the deficit

In short, deficiency in the nSR100 protein could explain the development of signs
and symptoms of autism in up to a third of cases. So, once the source of the disorder
has been identified, is there anything that could be done to correct this deficit? Well,
according to the authors, yes, and probably a lot.
As Benjamin Blencowe, co-director of the research, points out, "our animal model can
also be used as a testing field to evaluate molecules with the potential to reverse
nSR100 deficiency in autism. Instead of focusing on individual mutations linked to
autism, the identification of regulatory centers as nSR100 is much more effective. In
the future, with the increase of this protein, even minimal, in people with autism
we might be able to improve some of the behavioral deficits associated with the
disorder. "