Hydrogen peroxide can be generated by tau in the presence of Cu(II).
Alzheimer's disease has been closely related with oxidative stress, which might be responsible for the dysfunction or death of neuronal cells that contributes to disease pathogenesis. Impaired copper homeostasis makes contribution to the oxidative stress and consequently to several neurodegenerative conditions. Inappropriate binding of Cu(II) to cellular proteins are currently being explored as sources of pathological oxidative stress in several neurodegenerative disorders. Here we report that a fragment of tau protein possesses copper reduction activity and initiates the copper-mediated generation of hydrogen peroxide. The tau peptide was found to be oxidized to form disulfide bond-linked dimer. The hydrogen peroxide generated was quantified by TCEP/DTNB (tris(2-carboxyethyl) phosphine hydrochloride/5,5'-dithio-bis(2-nitrobenzoic acid). Since the copper reduction capacity and the generation of hydrogen peroxide were believe to be a major toxicological pathway of Abeta peptide, the functional similarity shared by tau and Abeta implies a new perspective of tau pathology.
Su
Xiao-Yang
XY
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, PR China.
Wu
Wei-Hui
WH
Huang
Zhi-Ping
ZP
Hu
Jia
J
Lei
Peng
P
Yu
Chun-Hui
CH
Zhao
Yu-Fen
YF
Li
Yan-Mei
YM
D003300:Copper / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000138:chemical synthesis*; D016875:tau Proteins / Q000737:chemistry*
D016875:tau Proteins; D003300:Copper; D006861:Hydrogen Peroxide