Pandey Gaurav, Morla Sudhir, Nemade Harshal B, Kumar Sachin, Ramakrishnan Vibin
Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati Guwahati-781039 India
Department of Electronics and Electrical Engineering, Indian Institute of Technology Guwahati Guwahati-781039 India.
RSC Adv. 2019 Feb 6;9(9):4744-4750. doi: 10.1039/c8ra09993f. eCollection 2019 Feb 5.
Toxic aggregation of tau protein to neurofibrillary tangles (NFTS) is a central pathological event involved in tauopathies. Inhibition of tau protein aggregation can serve as a straightforward therapeutic strategy. However, tau-based therapeutic solutions are not very common. Phenothiazine methylene blue (tau protein inhibitor) is currently the only drug under phase III clinical trials. In this work, a non-invasive strategy is presented for modulating the aggregation of core peptide segments of tau protein (VQIVYK and VQIINK) by using electric fields of varying strengths. We use thioflavin T staining, tyrosine fluorescence assay, electron microscopy, IR, dynamic and static light scattering, and neuronal toxicity estimation, for verifying the effect of electric field on the aggregation kinetics, morphology, conformational state and cellular toxicity of peptide systems. Our observations suggest that electric field arrests the self-assembly of VQIVYK and VQIINK fibrils thereby reducing the neurotoxicity instigated by them. Based on our observations, we propose a prospective scheme for a futuristic non-invasive therapeutic device.
tau蛋白毒性聚集形成神经原纤维缠结（NFTs）是tau蛋白病的核心病理事件。抑制tau蛋白聚集可作为一种直接的治疗策略。然而，基于tau蛋白的治疗方案并不常见。吩噻嗪亚甲蓝（tau蛋白抑制剂）是目前唯一处于III期临床试验阶段的药物。在这项工作中，我们提出了一种非侵入性策略，通过使用不同强度的电场来调节tau蛋白核心肽段（VQIVYK和VQIINK）的聚集。我们使用硫黄素T染色、酪氨酸荧光测定、电子显微镜、红外光谱、动态和静态光散射以及神经元毒性评估，来验证电场对肽系统聚集动力学、形态、构象状态和细胞毒性的影响。我们的观察结果表明，电场可阻止VQIVYK和VQIINK原纤维的自组装，从而降低它们引发的神经毒性。基于我们的观察结果，我们提出了一种未来非侵入性治疗设备的前瞻性方案。
