Mimosine functionalized gold nanoparticles (Mimo-AuNPs) suppress β-amyloid aggregation and neuronal toxicity  

作　　者：Bibin G.Anand Qi Wu Govindarajan Karthivashan Kiran P.Shejale Sara Amidian Holger Wille Satyabrata Kar 

机构地区：[1]Departments of Medicine and University of Alberta,Edmonton,Alberta,T6G 2M8,Canada [2]Centre for Prions and Protein Folding Diseases,University of Alberta,Edmonton,Alberta,T6G 2M8,Canada [3]Department of Metallurgical Engineering and Materials Science,Indian Institute of Technology Bombay,Powai,India [4]Departments of Biochemistry,University of Alberta,Edmonton,Alberta,T6G 2M8,Canada

出　　处：《Bioactive Materials》2021年第12期4491-4505,共15页生物活性材料（英文）

基　　金：This work was supported by grants from APRI-ASANT and CIHR(MOP-84480);SK and from APRI(APRI 201600028);HW.SynAD,University of Alberta provided a part of the postdoctoral fellowships for BGA,QW and KG.

摘　　要：Evidence suggests that increased level/aggregation of beta-amyloid(Aβ)peptides initiate neurodegeneration and subsequent development of Alzheimer’s disease(AD).At present,there is no effective treatment for AD.In this study,we reported the effects of gold nanoparticles surface-functionalized with a plant-based amino acid mimosine(Mimo-AuNPs),which is found to cross the blood-brain barrier,on the Aβfibrillization process and toxicity.Thioflavin T kinetic assays,fluorescence imaging and electron microscopy data showed that Mimo-AuNPs were able to suppress the spontaneous and seed-induced A_(1-42) aggregation.Spectroscopic studies,molecular docking and biochemical analyses further revealed that Mimo-AuNPs stabilize A_(1-42) to remain in its monomeric state by interacting with the hydrophobic domain of A_(1-42)(i.e.,Lys16 to Ala21)there by preventing a conformational shift towards theβ-sheet structure.Additionally,Mimo-AuNPs were found to trigger the disassembly of matured A_(1-42) fibers and increased neuronal viability by reducing phosphorylation of tau protein and the production of oxyradicals.Collectively,these results reveal that the surface-functionalization of gold nanoparticles with mimosine can attenuate Aβfibrillization and neuronal toxicity.Thus,we propose Mimo-AuNPs may be used as a potential treatment strategy towards AD-related pathologies.

关 键 词：Alzheimer’s disease β-amyloid aggregation Gold nanoparticles MIMOSINE NEUROPROTECTION 

分 类 号：R318.08[医药卫生—生物医学工程] TB383[医药卫生—基础医学]