title: Effects of macromolecular crowding and osmolyte on human Tau fibrillation.
abstract: Tau fibrillation is reported to be involved in neurodegenerative disorders, such as Alzheimer's disease, in which the natural environment is very crowded in the cells. Understanding the role of crowding environments in regulating Tau fibrillation is of great importance for elucidating the etiology of these diseases. In this experiment, the effects of macromolecular crowding and osmolyte reagents in the crowding environment on Tau fibrillation were studied by thioflavin T binding, SDS-PAGE and TEM assays. Ficoll 70 and Dextran 70 of different concentrations were used as macromolecular crowding reagents inside the cells and showed a strong enhancing effect on the fibrillation of normal and hyperphosphorylated Tau. The enhancing effect of Dextran is stronger than that of Ficoll 70 at the same concentration. In addition, the cellular osmolyte sucrose was found to protect Tau against fibrillation, and inhibit the enhancing effect of macromolecular crowding on Tau fibrillation. A possible model for the fibrillation process of Tau and the effect of macromolecular crowding and osmolyte on this process was proposed based on these experimental results. The information obtained from our study can enhance the understanding of how proteins aggregate and avoid aggregation in crowded physiological environments and might lead to a better understanding of the molecular mechanisms of Alzheimer's disease in vivo.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Gene Engineering and Biotechnology Beijing Key Laboratory, Beijing 100875, PR China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Gene Engineering and Biotechnology Beijing Key Laboratory, Beijing 100875, PR China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Teng
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Gene Engineering and Biotechnology Beijing Key Laboratory, Beijing 100875, PR China. Electronic address: lisen@bnu.edu.cn.
authors.forename: Sen
authors.initials: S
authors.lastname: Li
mesh_terms: D052160:Benzothiazoles; D003911:Dextrans / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005362:Ficoll / Q000494:pharmacology*; D005453:Fluorescence; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D012996:Solutions; D013395:Sucrose / Q000494:pharmacology; D013844:Thiazoles / Q000378:metabolism; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D052160:Benzothiazoles; D003911:Dextrans; D046911:Macromolecular Substances; D012996:Solutions; D013844:Thiazoles; D016875:tau Proteins; C009462:thioflavin T; D005362:Ficoll; D013395:Sucrose
keywords: Alzheimer's disease; Fibrillation; Macromolecular crowding; Osmolyte; Tau protein