There are various chromosomal abnormalities that babies can be born with, and Down syndrome (Trisomy 21) is one of the more common diagnoses. Down syndrome is caused when an individual has three copies of chromosome 21 rather than two copies (since one is normally inherited from each biological parent). There are a range of symptoms and health concerns that affected individuals can develop with some features encompassing differences in neurological development. A recent study from Kyoto University has uncovered a new set of protein interactions that are associated with differences in neurodevelopment and could help explain some of the features associated with Down syndrome, such as behavioral differences and intellectual disability.
In this study the authors further researched a protein called DYRK1A, which is found on chromosome 21 and is known to play an important role in neurodevelopment. It has previously been associated with intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder; however, its mechanism of action was largely unknown. The researchers focused on profiling where DYRK1A is specifically expressed in a cell and what other proteins it interacted with.
Down Syndrome is the result of having three copies of chromosome 21. Work to characterize the impact of DYRK1A protein interactions has shown a new mechanism that may explain features of intellectual disability seen in affected individuals.
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From this characterization the researchers discovered a new protein interaction in brain cells. A protein called FAM53C was found to bind to DYRK1A and repress the normal function of DYRK1A. When FAM53C binds to DYRK1A the protein (DYRK1A) does not become active and cannot move to activate other proteins in the cell nucleus that are involved in regulating cell division and making new brain cells. Essentially, an entire string of messages known as a signaling cascade is interrupted. This is thought to lead to incorrect expression of genes involved in the cell cycle. The researchers further hypothesized that this could contribute to incorrect amounts of DYRK1A protein being present in brain cells. Previous research has shown high levels of DYRK1A are associated with intellectual disability in Down syndrome.
At this time, further research is needed to better characterize the clinical significance of this interaction. A better understanding of processes that contribute to differences in neurodevelopment has large potential to translate to clinical research efforts to try and generate new types of therapies that can help with some of the symptoms individuals experience.
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