Authors: Lan Chen Yan Wei Xueqing Wang Rongqiao He
Publish Date: 2009/06/11
Volume: 66, Issue: 15, Pages: 2559-2571
Abstract
Although the glycation of Tau that is involved in paired helical filament formation in Alzheimer’s disease has been widely studied little attention has been paid to the role of dribose in the glycation of Tau Here we show that Tau is rapidly glycated in the presence of dribose resulting in oligomerization and polymerization Glycated derivatives appeared after 24 h incubation Western blotting indicated the formation of advanced glycation endproducts AGEs during initial stages of glycation Thioflavin Tpositive ThTpositive aggregations that appeared from day 4 indicated the globularlike features Atomic force microscopy revealed that the surface morphology of ribosylated Tau40 was globularlike Kinetic studies suggested that dribosylated Tau is slowly oligomerized and rapidly polymerized with ThTpositive features Moreover dribosylated Tau aggregates were highly toxic to SHSY5Y cells and resulted in both apoptosis and necrosis This work has demonstrated that dribose reacted with Tau protein rapidly producing ThTpositive aggregations which had high cytotoxicityWe thank Xinyong Chen Laboratory of Biophysics and Surface Analysis School of Pharmacy The University of Nottingham Nottingham NG7 2RD UK for his processing of AFM imaging This project was supported by the following grants NSFB06J11 NSFC30621004 973project2006CB500703 and CASKSCX2YWR119
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