Vanillin Benzothiazole Derivative Reduces Cellular Reactive Oxygen Species and Detects Amyloid Fibrillar Aggregates in Alzheimer's Disease Brain.
ACS chemical neuroscience(2023)
摘要
The misfolding of amyloid beta (Aβ) peptides into Aβ fibrillary aggregates is a major hallmark of Alzheimer's disease (AD), which responsible for the excess production of hydrogen peroxide (HO), a prominent reactive oxygen species (ROS) from the molecular oxygen (O) by the reduction of the Aβ-Cu(I) complex. The excessive production of HO causes oxidative stress and inflammation in the AD brain. Here, we have designed and developed a dual functionalized molecule VBD by using π-conjugation (C═C) in the backbone structure. In the presence of HO, the VBD can turn into fluorescent probe VBD-1 by cleaving of the selective boronate ester group. The fluorescent probe VBD-1 can undergo intramolecular charge transfer transition (ICT) by a π-conjugative system, and as a result, its emission increases from the yellow (532 nm) to red (590 nm) region. The fluorescence intensity of VBD-1 increases by 3.5-fold upon binding with Aβ fibrillary aggregates with a high affinity ( = 143 ± 12 nM). Finally, the VBD reduces the cellular toxic HO as proven by the CCA assay and DCFDA assay and the binding affinity of VBD-1 was confirmed by using in vitro histological staining in 8- and 18-month-old triple transgenic AD (3xTg-AD) mice brain slices.
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关键词
Alzheimer’s disease brain,H2O2,amyloid beta fibril,fluorescent probe
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