Investigation of the stability of the polyQ tract in the ATXN2 gene in the presence of CAA interruptions depending on the viscosity of the external

The ATXN2 gene plays a key role in the pathogenesis of neurodegenerative diseases such as spinocerebellar ataxia type 2 (SCA2). Expansion of trinucleotide repeats in the gene results in the formation of an abnormal protein with an extended polyglutamine strand, which is toxic to neu-rons and leads to their death. This disrupts the functioning of the cerebellum and other central nervous system structures, resulting in progressive deterioration of motor coordination and other neurological symptoms. Understanding the molecular basis of neurodegenerative processes caused by mutations in the ATXN2 gene, as well as the influence of environmental factors on disease development, remains an open question. Therefore, the aim of this study was to investi-gate the influence of the environment on the stability of the polyglutamine tract (polyQ) in the ATXN2 gene in the presence of a CAA interruption. The calculations were performed using an angular model of DNA, which considers the molecule as a system of interconnected pendulums, allowing for the influence of environmental viscosity on the dynamics of open states (OS) in DNA. The study was conducted at various viscosity values (λ = 0,9; 1,0; 1,1) and CAG tract lengths (from 35 to 55 repeats). The results showed that medium viscosity has a significant impact on polyQ tract stability, especially for CAG repeat lengths greater than 40. An increase in viscosity (λ = 1,1) contributed to a decrease in the number of additional OS zones, indicating its stabilizing role. Con-versely, a decrease in viscosity (λ = 0,9) increased the likelihood of OS formation, exacerbating tract instability. It was established that CAA insertions in the polyQ tract influence the formation of additional OS zones and CAG tract stability depending on their location. The results of this study provide a prerequisite for understanding the mechanisms regulating the structural stability of pro-teins associated with neurodegenerative diseases. The findings may lead to the development of more effective therapeutic strategies aimed at stabilizing abnormal polyQ tracts, potentially slowing the progression of diseases such as spinocerebellar ataxia and other polyglutamine pathologies.