| Abstract [eng] |
Transthyretin (TTR) is a tetrameric transport protein found in blood plasma and cerebrospinal fluid. It is primarily synthesized in the liver, as well as in the choroid plexus and the retinal pigment epithelium. TTR transports the thyroid hormone thyroxine (T4) and retinol (vitamin A) bound to retinol-binding protein. In transthyretin amyloidosis (TTRA), TTR amyloid fibrils accumulate in various organs and tissues, causing disease (most commonly amyloid polyneuropathy and cardiomyopathy) and death in patients. Transthyretin amyloidosis is classified into two main forms: hereditary transthyretin amyloidosis (pTTRA) and wild-type transthyretin amyloidosis (wtTTRA). The hereditary form is caused by mutations in the TTR gene, while the wild-type form is associated with aging and develops due to the accumulation of wild-type TTR. This study aims to evaluate the melting temperatures of the transthyretin pathogenic variants V30M and A97S to investigate their aggregation conditions. Since transthyretin amyloidosis is currently incurable and existing treatments only slow the progression of the disease, it is important to search for new compounds that could increase the effectiveness of treatment. During the study, the TTR variants V30M and A97S were purified using immobilized metal ion affinity and gel filtration chromatography. Protein stability was assessed by determining their melting temperatures using nano-differential scanning fluorimetry. It was found that the TTR A97S variant exhibits greater stability than TTR V30M. It was also found that the selected sulfonamide compounds had no significant effect on the stability of the TTR variants. Furthermore, by varying the aggregation conditions, the aggregation conditions were identified using an atomic force microscopy. |
