title: Glycation alter the process of Tau phosphorylation to change Tau isoforms aggregation property.
abstract: The risk of tauopathies depends in part on the levels and modified composition of six Tau isoforms in the human brain. Abnormal phosphorylation of the Tau protein and the shift of the ratio of 3R Tau to 4R Tau are presumed to result in neurofibrillary pathology and neurodegeneration. Glycation has recently been linked to dementia and metabolic syndrome. To determine the contribution of Tau protein glycation and phosphorylation on Tau aggregation propensity, the assembled kinetics were examined in vitro using Thioflavin T fluorescence assays. We found that glycation and phosphorylation have different effects on aggregation propensity in different Tau isoforms. Different Tau proteins play important parts in each tauopathies, but 3R0N, fetal Tau protein, has no effect on tauopathies. Conversely, 4R2N has more modified sites and a higher tendency to aggregate, playing the most important role in 4R tauopathies. Finally, Glycation, which could modulate Tau phosphorylation, may occur before any other modification. It also regulates the 3R to 4R ratio and promotes 4R2N Tau protein aggregation. Decreasing the sites of glycation, as well as shifting other Tau proteins to 3R0N Tau proteins has potential therapeutic implications for tauopathies.
authors.affiliation: School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, PR China.
authors.forename: Kefu
authors.initials: K
authors.lastname: Liu
authors.affiliation: Beijing Normal University, 19 Xinjiekouwai Street, Haidian District, Beijing 100875, PR China.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, PR China; School of Life Science, East China Normal University, 500 Dongchuan Road, Shanghai 200241, PR China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Li
authors.affiliation: Beijing Proteome Research Center, No.33, Life Science Park Road, Changping District, Beijing 102206, PR China.
authors.forename: Peibin
authors.initials: P
authors.lastname: Qin
authors.affiliation: School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, PR China.
authors.forename: Javed
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, PR China. Electronic address: deng@bit.edu.cn.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Deng
authors.affiliation: School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, PR China. Electronic address: hqing@bit.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Qing
mesh_terms: D006031:Glycosylation; D006801:Humans; D010766:Phosphorylation; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D024801:Tauopathies / Q000378:metabolism*; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D066329:Protein Aggregates; D020033:Protein Isoforms; D011994:Recombinant Proteins; D016875:tau Proteins
keywords: Glycation; Phosphorylation; Post-translational modification sites; Tau aggregation; Tau isoforms; Tauopathies