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 th...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.展开更多
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.
文摘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.
