Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, -781039, India.
Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, -781039, India.
Neuropeptides. 2020 Jun;81:102030. doi: 10.1016/j.npep.2020.102030. Epub 2020 Feb 25.
Abnormal aggregation of beta-amyloid (Aβ) peptide into amyloid plaques in the brain has been identified as one of the key factors in instigating AD pathogenesis. Inhibition of Aβ aggregation can be an important therapeutic strategy in disease management. In this work, we demonstrate the application of structure-based design of short peptides ('trojan peptides'), intended to intervene in the aggregation of the core recognition domain of amyloid-beta peptide, a known malefactor in Alzheimer's disease. The modulatory effect of trojan peptides has been assessed using ThT fluorescence assay, FETEM imaging, IR, and toxicity assays on model neuronal cell lines. Experimental results suggest that designed trojan peptides could impede the aggregation of the core amyloid fibril forming segment of Aβ peptide, arrest the formation of toxic fibrillar assemblies, and reduce cytotoxicity of the neuronal cell lines.
β-淀粉样蛋白（Aβ）肽在大脑中异常聚集形成淀粉样斑块已被确定为引发 AD 发病机制的关键因素之一。抑制 Aβ聚集可以成为疾病管理中重要的治疗策略。在这项工作中，我们展示了基于结构设计的短肽（“木马肽”）的应用，旨在干预淀粉样β肽核心识别域的聚集，这是阿尔茨海默病的已知罪魁祸首。木马肽的调节作用已通过 ThT 荧光测定法、FETEM 成像、IR 和对模型神经元细胞系的毒性测定来评估。实验结果表明，设计的木马肽可以阻止 Aβ肽核心原纤维形成片段的聚集，阻止有毒纤维状组装的形成，并降低神经元细胞系的细胞毒性。
