Department of Biology, Faculty of Basic Sciences, Lorestan University, Khorramabad, Iran.
Research Center of Oils and Fats, Research Institute for Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
J Biomol Struct Dyn. 2024;42(23):12761-12775. doi: 10.1080/07391102.2023.2273433. Epub 2023 Oct 25.
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 . 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 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 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.
tau 蛋白以成对螺旋丝（PHF）的形式聚集导致微管结构的破坏和神经退行性疾病的发展，如阿尔茨海默病。因此，抑制 tau 蛋白聚集是预防这些疾病进展的潜在策略。在这项研究中，磺胺甲恶唑（SMZ）是一种容易穿过血脑屏障并与 tau 蛋白相互作用的抗生素，其抑制 tau 聚集的能力得到了测试。采用了包括 XRD、LDH 细胞毒性比色测定和显微镜成像在内的各种多光谱技术。结果表明，SMZ 通过氢键和范德华相互作用与 tau 蛋白有效相互作用。它还能有效抑制 tau 蛋白聚集，并显著降低 SH-SY5Y 神经母细胞瘤细胞系的毒性。分子对接和 MD 模拟结果表明，SMZ 可能通过与 PHF6 基序相互作用来减少 tau 蛋白聚集。总的来说，这些发现表明，SMZ 作为 tau 蛋白聚集抑制剂具有治疗潜力，至少在某些条件下是这样。这些发现表明，SMZ 有可能成为治疗涉及 tau 蛋白聚集的神经退行性疾病的药物。然而，需要进一步的研究来证实这些结果，并评估 SMZ 在动物模型和临床试验中的有效性。由 Ramaswamy H. Sarma 交流。
