中文摘要
与脑神经退行性疾病有关的老年痴呆症、帕金森病、朊蛋白病等已成为当今危害人类健康的重要杀手。但人们对其致病机理尚不清楚,更缺乏有效的治疗手段。基于该疾病均表现出由于蛋白质的错误折叠而导致的淀粉状蛋白聚集沉淀,并且它们的某些保守性氨基酸序列及淀粉状沉淀形成的动力学过程与对应的家蚕丝素蛋白的氨基酸序列及其纤维化吐丝过程有惊人的相似之处,因此本项目提出用自然界易于获得且较稳定的丝素蛋白作为模型化合物对该疾病致病机理及中药治疗进行探索性研究。利用先进的谱学方法,如核磁共振、顺磁共振、拉曼光谱、圆二色谱、荧光光谱等,以及量子化学计算、分子动力学计算等,研究环境变化,如pH、金属离子、蛋白质浓度、中药试剂,对蛋白质错误折叠的诱导、干扰、控制及清除机理研究。并且,拟将经优化及分类的实验条件及药物用于对模型病鼠的研究。以期获得对此类疾病的致病机理和治疗方法的更多了解。
英文摘要
Neurodegenerative diseases, such as Alzheimer's disease, Parkinson disease, Creutzfeldt-Jakob disease, etc, have become important killers to human being. However the mechanism and therapies for these diseases are still unclear. There exist amyloidal peptide miss-folding and conformation transition mechanism from helix type to ?-sheet type and similar conservative peptide sequences in the proteins related to these diseases. Interestingly, silk fibroin has also strikingly similarity in its interesting polypeptide and conformation change during spinning. Therefore, we attempt here to use silk fibroin which is easily obtained ant stable naturally as model protein to investigate the mechanism and Chinese herb therapy for these diseases. Many spectroscopy and calculation methods, for example, NMR, EPR, Raman, CD, fluorescence, quantum chemistry and molecular dynamics, will be applied to study environment influences on protein folding and un-folding processes under various conditions of pH, metal ions, protein concentration, and Chinese herbs. Furthermore, animal testing will also be performed. Hopefully, the work would make us understand more about these disease and therapy methods.
结题摘要
与脑神经退行性疾病有关的老年痴呆症、帕金森病、朊蛋白病等已成为当今危害人类健康的重要杀手。但人们对其致病机理尚不清楚,更缺乏有效的治疗手段。基于该疾病均表现出由于蛋白质的错误折叠而导致的淀粉状蛋白聚集沉淀,并且它们的某些保守性氨基酸序列及淀粉状沉淀形成的动力学过程与对应的家蚕丝素蛋白的氨基酸序列及其纤维化吐丝过程有惊人的相似之处,因此本项目提出用自然界易于获得且较稳定的丝素蛋白作为模型化合物对该疾病致病机理及中药治疗进行探索性研究。利用先进的谱学方法,如核磁共振、顺磁共振、拉曼光谱、圆二色谱、荧光光谱等,以及量子化学计算、分子动力学计算等,研究环境变化,如pH、金属离子、蛋白质浓度、中药试剂,对蛋白质错误折叠的诱导、干扰、控制及清除机理研究。并且,拟将经优化及分类的实验条件及药物用于对模型病鼠的研究。以期获得对此类疾病的致病机理和治疗方法的更多了解。
