On the occasion of Rare Disease Day, the Biofisika Institute (CSIC, EHU) presents the progress of a project aimed at understanding the molecular origins of the neurodevelopmental syndrome CTNNB1, a rare disease caused by mutations in the beta-catenin protein. Although less than 50 cases of this pathology have been diagnosed in Spain, rare diseases affect a total of almost three million people.
The study is led by Sonia Bañuelos, researcher at the Biofisika Institute and lecturer at the Department of Biochemistry and Molecular Biology at the University of the Basque Country (EHU).
“Our goal is to understand how these mutations prevent the proper formation of the brain. Understanding the mechanisms at the molecular level is necessary to develop specific treatments in the future,” emphasizes the scientist.
The project is carried out in collaboration with a neuropsychology team from the University of Deusto – pioneers in the study of the disease – molecular geneticists from the Biobizkaia Institute at the Cruces University Hospital and the brain organoid platform at the Achucarro Neuroscience Center. The Spanish Patient Association CTNNB1, based in Bizkaia, is also actively involved in the initiative.
An essential protein for proper brain development
Beta-catenin is essential during embryonic development and also in the adult organism. One of its functions is related to cell adhesion, which imparts cohesion and mechanical strength to tissues. These processes are fundamental in the formation of the brain and in the stabilization and plasticity of synapses, the basis of learning and memory.
In CTNNB1 syndrome, most mutations create incomplete or misfolded proteins that cannot perform their function. This dysfunction alters critical processes in brain development.
AI, biophysics and brain organoids to study a rare syndrome
The Biofisika Institute team uses tools based on the three-dimensional structure of proteins to predict how these mutations affect the interaction between beta-catenin and cadherin, key components of cell adhesion complexes.
Predictions are verified in the laboratory using biophysical techniques. To do this, mutant versions of the protein corresponding to real cases identified in the Spanish cohort are produced in bacteria. Brain organoids allow more precise modeling of how these changes affect the development of neural tissue.
Although this is basic research, the results “could help in the future development of rationally designed therapies.”
Sonia Bañuelos, researcher, Biofisika Institute and lecturer, Department of Biochemistry and Molecular Biology, University of the Basque Country
Supporting research into rare diseases
“Understanding the mechanisms of a disease is the first step towards finding a cure. That’s why rare disease research is essential,” emphasizes the researcher.
On the occasion of Rare Disease Day, the Biofisika Institute recalls the importance of promoting research into these minority diseases, which have a huge impact on those who experience them firsthand.
