In Vitro Studies on Accelerating the Degradation and Clearance of Amyloid-β Fibrils by an Antiamyloidogenic Peptide

被引：13

作者：

Zhang, Qian ^{[1
]}

Liu, Jing ^{[1
]}

Hu, Xiaoyu ^{[1
]}

Wang, Wei ^{[1
]}

Yuan, Zhi ^{[1
]}

机构：

[1] Nankai Univ, Key Lab Funct Polymer Mat, Minist Educ, Inst Polymer Chem,Collaborat Innovat Ctr Chem Sci, Tianjin 300071, Peoples R China

来源：

ACS MACRO LETTERS | 2015年 / 4卷 / 04期

基金：

中国国家自然科学基金;

关键词：

ALZHEIMERS-DISEASE; A-BETA; MICROGLIAL CELLS; AGGREGATION; MECHANISM; PROTEIN; CYTOTOXICITY; A-BETA(1-40); PATHOGENESIS; INHIBITION;

D O I：

10.1021/acsmacrolett.5b00033

中图分类号：

O63 [高分子化学（高聚物）];

学科分类号：

070305 ; 080501 ; 081704 ;

摘要：

The clearance of overloaded amyloid-beta (A beta) species, especially the toxic aggregates, was thought to be an attractive and promising strategy for Alzheimer's disease (AD) therapy in the past decade. In this work, an active A beta inhibitor decapeptide RR was used to transform mature A beta fibrils (fA beta) into nanorod-like A beta assemblies (rA beta) as well as loosen the beta-structure of rA beta. Compared with fA beta, rA beta could be engulfed by PC12 cells more efficiently and showed a 1.46-fold difference. More importantly, the rA beta was colocated with lysosomes after endocytosis, and in vitro study illustrated that rA beta were easily degraded by lysosome protease cathepsin B when compared with the fibrils. Thus, our study indicated the potential application of RR in A beta fibrils clearance by a cell-participated and enzyme-mediated pathway.

引用

页码：339 / 342

页数：4

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