Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1862, Issue 2, Pages 192-201Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2015.12.002
Keywords
Tau isoforms; Tauopathies; Tau aggregation; Glycation; Phosphorylation; Post-translational modification sites
Funding
- National Natural Science Foundation of China [81171206]
- Ministry of Science and Technology in China [2013YQ03059514]
Ask authors/readers for more resources
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 3RON Tau proteins has potential therapeutic implications for tauopathies. (C) 2015 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available