Au23(CR)14 nanocluster restores fibril Aβ's unfolded state with abolished cytotoxicity and dissolves endogenous plaques

• 来源期刊: 国家科学评论（英文版）
• 关键词: gold nanoclusters Alzheimer's disease restores fibril Aβ's unfolded state abolished cytotoxicity dissolves endogenous Aβ plaques
• 年，卷（期）: 2020,（4）
• 页码范围: 763-774
• 页数: 12页
• 语种: 英文
• DOI: 10.1093/nsr/nwz215

摘要

The misfolding of amyloid-β (Aβ) peptides from the natural unfolded state toβ-sheet structure is a critical step,leading to abnormal fibrillation and formation of endogenous Aβ plaques in Alzheimer's disease (AD).Previous studies have reported inhibition of Aβ fibrillation or disassembly of exogenous Aβ fibrils in vitro.However,soluble Aβ oligomers have been reported with increased cytotoxicity;this might partly explain why current clinical trials targeting disassembly of Aβ fibrils by anti-Aβ antibodies have failed so far.Here we show that Au23 (CR) 14 (a new Au nanoduster modified by Cys-Arg (CR) dipeptide) is able to completely dissolve exogenous mature Aβ fibrils into monomers and restore the natural unfolded state of Aβ peptides from misfoldedβ-sheets.Furthermore,the cytotoxicity of Aβ40 fibrils when dissolved by Au23 (CR)14 is fully abolished.More importantly,Au23 (CR) 14 is able to completely dissolve endogenous Aβ plaques in brain slices from transgenic AD model mice.In addition,Au23 (CR)14 has good biocompatibility and infiltration ability across the blood-brain barrier.Taken together,this work presents a promising therapeutics candidate for AD treatment,and manifests the potential ofnanotechnological approaches in the development of nanomedicines.