Spanish researchers have found a key that could explain up to 80% of cases of autism, known as “idiopathic autism.” The authors, from the Barcelona Biomedical Research Institute, have achieved open a door to new therapeutic targets against the disease.
Autism is a neurodevelopmental condition related to difficulty acquiring communication and social interaction skills. “About 20% of cases are linked to a specific genetic mutation, but the origin of the remaining 80% remains a mystery.“they emphasize from the research center.
Thus, the finding suggests that the lack of a segment in a protein, CPEB4, decreases the expression of genes that are crucial for neuronal development. Already in 2018, it had been found that in people with autism a neuron-specific microexon (short fragment of DNA) was lost in the CPEB4 protein. The work, published in the magazine Nature, reveals why this small segment is essential for CPEB4 activity in the brain.
“In this work we discovered that this neuronal microexon is essential to maintain the stability and dynamics of the condensates formed by CPEB4 in neurons. Without the microexon, the condensates become less dynamic and can form solid aggregates that do not function properly,” he explains. Dr. Xavier Salvatella, ICREA researcher and head of the Molecular Biophysics laboratory at IRB Barcelona.
This work, therefore, provides new perspectives on how small modifications in the proteins that regulate gene expression can have a “determining” impact on neuronal development, as added by Dr. Raúl Méndez, researcher and head of the Translational Control laboratory. of Cell Cycle and Differentiation from IRB Barcelona.
Thus, both explain that the correct regulation of these genes is “essential” during brain development. If the protein condensates do not function well due to the lack of the neuronal microexon, alterations occur in neuronal development that manifest as symptoms of autism. The described mechanism explains the complexity of idiopathic autism and its heterogeneous nature as well, since this spectrum includes multiple manifestations and degrees of severity.
“Our results suggest that even small decreases in microexon inclusion can have significant effects. This could explain why some people develop idiopathic autism without a genetic mutation,” explain doctors Carla Garcia-Cabau and Anna Bartomeu, researchers at the IRB Barcelona and first authors of the work.
The study is still in its early stages, but the researchers are “hopeful” as this milestone provides insight into a possible therapeutic approach that restores CPEB4 function. However, the study still needs to undergo more experimental tests, such as studies in animal models.
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