The deposition of highly ordered amyloid fibrils is recognized as a hallmark of amyloidosis diseases such as Alzheimer’s disease and Parkinson’s disease.Disaggregating the amyloid fibrils is considered as one of the...The deposition of highly ordered amyloid fibrils is recognized as a hallmark of amyloidosis diseases such as Alzheimer’s disease and Parkinson’s disease.Disaggregating the amyloid fibrils is considered as one of the effective strategies for the control and treatment of amyloidosis diseases.In this article,by simulating the function of natural molecular chaperones,co-assembled block copolymer micelles with coordination groups of nitrilotriacetic acid(NTA)and hydrophobic microdomains of poly(Nisopropylacrylamide)(PNIPAM)on the surface were used as nanochaperones(n Chaps)to disaggregate amyloid insulin fibrils.Zinc ions chelated by NTA can bind the histidine imidazole residues while the PNIPAM microdomains can interact with the exposed hydrophobic sites on the amyloid insulin fibrils,which synergistically perturb the stability of amyloid insulin fibrils,loosen their structure,and finally promote their disaggregation.A combination of characterizations with fluorescence spectroscopy,transmission electron microscopy(TEM),dynamic hight scattering(DLS),and quartz crystal microbalance(QCM)demonstrated that mature amyloid insulin fibrils were completely disaggregated after incubating with n Chaps for 90 h.This study may provide a promising strategy for the development of n Chaps for the treatment of amyloidosis diseases.展开更多
基金supported by the National Natural Science Foundation of China(51773099,51933006)。
文摘The deposition of highly ordered amyloid fibrils is recognized as a hallmark of amyloidosis diseases such as Alzheimer’s disease and Parkinson’s disease.Disaggregating the amyloid fibrils is considered as one of the effective strategies for the control and treatment of amyloidosis diseases.In this article,by simulating the function of natural molecular chaperones,co-assembled block copolymer micelles with coordination groups of nitrilotriacetic acid(NTA)and hydrophobic microdomains of poly(Nisopropylacrylamide)(PNIPAM)on the surface were used as nanochaperones(n Chaps)to disaggregate amyloid insulin fibrils.Zinc ions chelated by NTA can bind the histidine imidazole residues while the PNIPAM microdomains can interact with the exposed hydrophobic sites on the amyloid insulin fibrils,which synergistically perturb the stability of amyloid insulin fibrils,loosen their structure,and finally promote their disaggregation.A combination of characterizations with fluorescence spectroscopy,transmission electron microscopy(TEM),dynamic hight scattering(DLS),and quartz crystal microbalance(QCM)demonstrated that mature amyloid insulin fibrils were completely disaggregated after incubating with n Chaps for 90 h.This study may provide a promising strategy for the development of n Chaps for the treatment of amyloidosis diseases.
