Negatively charged gold nanoparticles inhibit Alzheimer's amyloid-β fibrillization, induce fibril dissociation, and mitigate neurotoxicity.
Amyloids are pathogenic hallmarks in many neurodegenerative diseases such as amyloid-β (Aβ) fibrils in Alzheimer's disease (AD). Here, the effect of gold nanoparticles (AuNPs) on amyloids is examined using Aβ as a model system. It is found that bare AuNPs inhibited Aβ fibrillization to form fragmented fibrils and spherical oligomers. Adding bare AuNPs to preformed Aβ fibrils results in ragged species where AuNPs bind preferentially to fibrils. Similar results are demonstrated with carboxyl- but not amine-conjugated AuNPs. Co-incubation of negatively charged AuNPs with Aβ relieved Aβ toxicity to neuroblastoma. Overall, it is demonstrated that AuNPs possessing negative surface potential serve as nano-chaperones to inhibit and redirect Aβ fibrillization, which could contribute to applications for AD.
Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Yi-Hung
YH
Liao
Yu-Jen
YJ
Chang
Yuji
Y
Yoshiike
Yun-Chorng
YC
Chang
Yun-Ru
YR
Chen
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D002470:Cell Survival; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D000682:Amyloid; D016229:Amyloid beta-Peptides; D006046:Gold