The latest paper by the Academy of Biological Sciences of Wuhan University reveals the molecular mechanism of zinc ions regulating Tau protein phase separation and cytotoxicity

On April 19, the International Journal of Biological Macromolecules (impact factor 6.

Preliminary work on protein disulfide isomerase (PDI) and myricetin regulating Tau protein phase separation, autophagy and toxicity (published in Journal of Molecular Biology and Journal of Molecular Biology on March 27, 2020 and September 22, 2021, respectively of Biological Chemistry ), Professor Liang Yi's research team revealed the regulatory mechanism of PDI on the formation, aggregation and toxicity of Tau protein droplets and its role in AD, and explained that PDI and its thiol nitrosylation regulate Tau phase separation And the molecular mechanism of the disease is found.

In this study, Prof.

The findings of this work reveal for the first time the regulatory mechanism of zinc ions on Tau droplet formation, mitochondrial damage, and Tau protein toxicity in cells, elucidating the role of zinc homeostasis and Tau protein phase separation in AD pathogenesis, so zinc As a negative regulator of neurodegenerative diseases such as AD, ions play an important role in promoting the liquid-liquid phase separation of Tau and aggravating the mitochondrial damage caused by Tau aggregation, providing a new perspective for the targeted therapy of AD with inorganic ions, and also for the treatment of AD.

Wuhan University is the first signatory unit, Gao Yingying, a 2018 doctoral student of the School of Life Sciences, is the first author, Zhong Tao, a 2021 doctoral student, is the co-first author, and Professor Liang Yi is the corresponding author

▲ Zinc ions promote the co-localization of Tau protein and G3BP1 in cells

▲ Zinc ions promote the interaction between Tau protein and G3BP1

▲ Zinc ions exacerbate Tau aggregation-induced mitochondrial damage and up-regulation of reactive oxygen species (ROS)

Paper link: https://doi.