title: D-Ribosylated Tau forms globular aggregates with high cytotoxicity.
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 D-ribose in the glycation of Tau. Here, we show that Tau is rapidly glycated in the presence of D-ribose, resulting in oligomerization and polymerization. Glycated derivatives appeared after 24 h incubation. Western blotting indicated the formation of advanced glycation end-products (AGEs) during initial stages of glycation. Thioflavin T-positive (ThT-positive) aggregations that appeared from day 4 indicated the globular-like features. Atomic force microscopy revealed that the surface morphology of ribosylated Tau40 was globular-like. Kinetic studies suggested that D-ribosylated Tau is slowly oligomerized and rapidly polymerized with ThT-positive features. Moreover, D-ribosylated Tau aggregates were highly toxic to SHSY5Y cells and resulted in both apoptosis and necrosis. This work has demonstrated that D-ribose reacted with Tau protein rapidly, producing ThT-positive aggregations which had high cytotoxicity.
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, 100101 Beijing, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Wei
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.forename: Rongqiao
authors.initials: R
authors.lastname: He
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles; D002460:Cell Line; D005456:Fluorescent Dyes / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000378:metabolism; D011487:Protein Conformation; D012266:Ribose / Q000737:chemistry / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity
chemical_list: D052160:Benzothiazoles; D005456:Fluorescent Dyes; D013844:Thiazoles; D016875:tau Proteins; C009462:thioflavin T; D012266:Ribose