Peptide-decorated Gold Nanoparticles Inhibit Mutant Huntingtin Protein Aggregation

• Main Authors: HO, YU-JUNG, 何昱瑢
• Other Authors: Huang, Jen-Tse
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/5u2uw9

碩士 === 國立中正大學 === 化學暨生物化學研究所 === 105 === Huntington’s disease(HD) is an neurodegenerative disease caused by an expansion of trinucleotide(CAG) repeats in the HD(IT15) gene which result in an aggregation-prone mutant Huntingtin protein(mHtt). Generally, people who have less than 36 repeats glutamine are classified as normal. However, the number of glutamines residue in the neuron of HD patients is greater than 40. The expansion of polyglutamine is prone to form aggregates and induce cytotoxicity in the cell. Here we have designed a series of therapeutic peptides consisting of polyglutamine which can recognize mHtt protein and poly charge sequences [poly-glutamate (CG3E6Q10), poly- serine (CG3S6Q10) and poly-arginine (CG3R6Q10)]. We further decorated these peptides on the surface of gold nanoparticles (AuNPs) through the binding between cysteine and gold. Unfortunately, the incorporation of AuNPs with CG3S6Q10 and CG3R6Q10, respectively, resulted in severe AuNPs aggregation thus we discarded these two peptides. The incorporation of AuNPs with CG3E6Q10 could largely prevent the in vitro amyloidogenesis process of the amyloidogenic peptides and even dissociate preformed amyloid fiber in a concentration dependent manner. In addition, for in vivo study, in the presence of polyethyleneimine, these surfaced-decorated AuNPs allow to penetrate cells and dissociate cytosolic aggregates from the eYFP-tagged mutant Huntingtin protein.