The Degradation And Interaction Of Amyloid Aggregates

The excessive production and accumulation of amyloid proteins in the human body is considered to be closely related to the pathegenesis of many neurodegenerative diseases.At present,there is no effective means to detect and treat neurodegenerative diseases in an early period.For the treatment of such diseases,one is to inhibit the abnormal aggregation of amyloid protein and the other is to effectively degrade the existed amyloid plaques.Notely,the degradation of amyloid aggregates is far more difficult than inhibiting the aggregation of amyloid protein.Therefore,the development of drugs and methods for degrading amyloid aggregates has urgent practical needs and scientific significance.In this thesis,we firstly explored the degradation of amyloid protein in photodynamic therapy by GO/g-C₃N₄ and Au/g-C₃N₄ composite materials,and discusses the mechanism of the composite materials.Finally,amylin species induced the aggragation of Aβwere explored.The details are as follows:1.The photodegradation and degradation efficiency of GO/g-C₃N₄ composite on Aβ33-42 aggregates.First synthesize GO/g-C₃N₄ composite material,GO asβ-amyloid protein adsorbent,g-C₃N₄ as catalytic degradation reagent,the synergy of the two can improve the photocatalytic degradation ability of the material.Secondly,the GO/g-C₃N₄ composite material under the 365 nm ultraviolet light was used to photo-degrade the Aβ33-42 fiber aggregates,with the height of the amyloid fibrils was reduced from8.5±0.5 nm to 3.5±0.5 nm,and the fiber coverage decreased from 28.3±3.4%to 3.3±0.6%,indicating that the composite material GO/g-C₃N₄ can efficiently degrade Aβ33-42 with UV.After the degradation,the decrease in the Young’s modulus of the aggregate indicated that the protein aggregate fibrils has changed significantly.Finally,the analysis of active oxygen radical scavenging experiments discussed the degradation mechanism of the composite material,and the cytotoxicity of the GO/g-C₃N₄composite material was investigated.2.Based on g-C₃N₄ gold nanoparticle modified g-C₃N₄ was developed and applied to the degradation of amylin.Firstly,Au/g-C₃N₄ composite material was synthesized.In surface plasmon resonance,gold nanoparticles can increase light absorption and stimulate g-C₃N₄ to generate electron-pair pairs,increasing free radicals and improving photodegradation efficiency.Secondly,with photodegradation of the amylin 20-29 aggregates by Au/g-C₃N₄,the height of fibrils of the aggregates changed from 32.8±0.3 nm to 15.8±0.6 nm after degradation.The composite material Au/g-C₃N₄ effectively degraded the amylin 20-29 aggregate fiber and the Young’s modulus of the degraded aggregate decreased indicating that the protein aggregate fibrils has changed.Finally,the DCFH-DA fluorescence experiment was used to explore the mechanism of action of the composite material.3.Finally,we explored the effect of amylin on the aggregation process ofβ-amyloid peptides.Firstly,the addition of amylin peptide significantly increased theβ-sheet content inβ-amyloid peptides.Secondly,the height of Aβ1-40 fibrils incubated alone for 48h was 3.2±1.0 nm,after the addition of hIAPP1-37（monomer,oligomer,short fiber,fiber）the average height of Aβ1-40 fibrils was 14.5±2.0 nm,5.0±0.9 nm,11.3±2.2 nm and 6.4±0.4 nm,respectively,and membrane structure appeared after hIAPP1-37 short fiber co-incubated with Aβ1-40.Finally,we explored the changes in the mechanical properties of Aβ1-40 aggregates.The Young’s modulus of co-aggregatesof hIAPP1-37 and Aβ1-40 was higher than the pristine Aβ1-40 aggregates,but presenting the decreased adhesion relatively.Generally,short fibers of hIAPP1-37displayed the robust effect on Aβ1-40 Young’s modulus and adhesion.