Regulation Of Assembly Structure Of Amyloid-? Peptide And Degradation Of Its Aggregates

Years of research have shown that excessive production and deposition of amyloid-?protein is considered to be one of the characteristics of some degenerative diseases,such as Alzheimer's disease,Down's syndrome and hereditary cerebral hemorrhage.Alzheimer's disease is the most common type of Alzheimer's disease.Its pathogenesis is that amyloid-?protein?A??aggregates to form oligomers,fibrils and plaques,which cause neurotoxicity and neurodegeneration.The amyloid plaque formed by amyloid-?protein is mainly composed of fibrils,which are mainly aggregated by A?1-42 peptide,and A?16-20 peptide is the key segment of A?1-42protofibrosis.Therefore,it is urgent to find effective methods to degrade and regulate the aggregation of amyloid-?protein.In this paper,the degradation and degradation efficiency of porphyrin on the aggregates of amyloid-?peptide,the assembly and difference of amyloid-?peptide regulated by glow discharge,and the preparation of precious metal-peptide composites by glow discharge with HAuCl₄ were studied.We found that porphyrin can degrade A?1-42 aggregates under light-driven conditions,and its degradation efficiency can be obtained.Glow discharge can regulate the assembly of A?16-20 and its terminal modified peptide into thin film structure,and further successfully prepare the composite material of amyloid-?peptide and precious metal.This discovery provides some guidance and theoretical basis for the development of new drugs and new control methods for the treatment of Alzheimer's disease in the future.Specific research contents are as follows:1)The degradation of A?1-42 aggregates by light-driven porphyrins and their degradation efficiency were studied.Firstly,the dynamic process of self-assembled fibrosis of A?1-42 was studied.Fiber aggregates were obtained by incubating peptides at 37?for 72 h.The conditions of forming fibrils of A?1-42 were explored by atomic force microscopy.Quartz crystal microbalance was used to evaluate the degradation of A?1-42 fibrils by light-driven porphyrins,and its degradation efficiency was quantitatively obtained.When the concentration of porphyrins was 1?M,2.5?M and 5?M,the degradation efficiency was 72%,77%and 90%,respectively.The degradation of porphyrins was investigated by atomic force microscopy,circular dichroism and ThT fluorescence labeling.The results show that photodriven porphyrins can degrade mature A?1-42 fibrils into short fibrils or even granules.2)The regulation of the assembly structure of A?16-20 before and after terminal modified by glow discharge and its differences were studied.KLVFF-NH₂and Ac-KLVFF were prepared by amination and amidation of terminal groups of A?16-20?KLVFF?.A?16-20 was incubated at different time before and after modification by glow discharge.The morphology of aggregates was characterized by atomic force microscopy?AFM?and their height was analyzed.Finally,the secondary structure of aggregates was analyzed by circular dichroism.The results show that glow discharge can significantly regulate the assembly structure of three segments of peptide before and after modification of A?16-20.Self-assembly can form film structure.The film height is 7.3±1.2 nm,3.5±0.2 nm and 5.4±0.7 nm,respectively.The roughness of the three film structures is the largest in KLVFF-NH₂ and the smallest in KLVFF.Without glow discharge treatment,no film structure can be formed.It is suggested that glow discharge can regulate the assembly structure of A?16-20 and its terminal modified peptide,and the film structure formed by glow discharge is also different.3)In addition,on the basis of the previous chapter,the preparation of precious metal-peptide composites by glow discharge-regulated A?16-20 and its terminal modified peptide and HAuCl₄ was studied.A?16-20 and its terminal modified peptides were mixed with HAuCl₄ solution respectively.After glow discharge treatment,they were incubated at 37?for 168 h,and characterized by transmission electron microscopy?TEM?and ultraviolet spectrophotometer.The results show that gold nanoparticles can be formed on the surface of peptide films after glow discharge treatment.Compared with the three kinds of gold nanoparticles-film composites,the gold nanoparticles film composites formed by KLVFF-NH₂ and HAuCl₄ are the best.A single layer of uniform and compact gold nanoparticles are formed on the surface of the films.The ultraviolet absorption characteristic peaks are analyzed.The formation of gold nanoparticles has also been confirmed,and significant inhibition of A?1-42aggregation.