Genesis of additional open state zones in the extended polyQ tract of the ATXN2 gene depends on its length and interruptions localization

The ATXN2 gene is located on chromosome 12q24.1 and encodes the ataxin-2 protein, which is involved in the regulation of RNA metabolism, protein synthesis, and intracellular signaling. The polyQ tract encoding glutamine can expand, which leads to the development of various neurodegenerative diseases. CAA interruptions play an important role in stabilizing the polyQ tract in the ATXN2 gene. However, CAA interruptions may be associated with other neurodegenerative conditions such as parkinsonism. In this paper, the stability of the polyQ tract in the presence of CAA interruptions depending on their localization was studied using mathematical modeling methods. It was found that interruptions located near the center of the polyQ tract significantly reduce its stability, and those located near its borders can both reduce and increase the stability of the polyQ tract. In this case, a certain asymmetry is observed: CAA interruptions located near the left border of the polyQ tract have a more stabilizing effect than CAA interruptions located near the right border. © 2025 Elsevier B.V., All rights reserved.