The induction of tau aggregation is restricted by sulfamethoxazole and provides new information regarding the use of the drug

Abstract

The aggregation of tau protein in the form of paired helical filament (PHF) leads to the breakdown of microtubule structure and the development of neurodegenerative disorders, such as Alzheimer’s disease. Therefore, inhibiting tau protein aggregation is a potential strategy for preventing the progression of these disorders. In this study, sulfamethoxazole (SMZ), an antibiotic that easily crosses the blood-brain barrier and interacts with tau protein, was tested for its ability to inhibit tau aggregation in vitro. Various multi-spectroscopic techniques including XRD, LDH cytotoxicity colorimetric assay, and microscopic imaging were employed. The results showed that SMZ effectively interacts with tau protein through hydrogen and van der Waals interactions. It also effectively inhibited tau protein aggregation in vitro and significantly reduced toxicity in the SH-SY5Y neuroblastoma cell line. Molecular docking and MD simulation results suggested that SMZ may reduce tau protein aggregation by interacting with the PHF6 motif. Overall, these findings indicate that SMZ has therapeutic potential as a tau protein aggregation inhibitor, at least under in vitro conditions. These findings suggest that SMZ has potential as a treatment for neurodegenerative disorders involving tau protein aggregation. However, further research is needed to confirm these results and assess the effectiveness of SMZ in animal models and clinical trials. Communicated by Ramaswamy H. Sarma