4.8 Article

High-Performance Extended-Gate Field-Effect Transistor for Kinase Sensing in Aβ Accumulation of Alzheimer's Disease

期刊

ANALYTICAL CHEMISTRY
卷 94, 期 2, 页码 1491-1497

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.1c05164

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资金

  1. National Natural Science Foundation of China [21775044]
  2. Shanghai Science and Technology Committee [19ZR1473300, 18DZ1112700]
  3. Fundamental Research Funds for the Central Universities

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Exploring the upstream and downstream relationship of Aβ in Alzheimer's disease (AD) is of great significance. In this study, a peptide-functionalized EG-FET sensor was developed to monitor c-Abl level with high sensitivity and selectivity. The sensor was successfully used to quantify c-Abl activity in AD transgenic mice and explore the interaction between c-Abl and Aβ.
An amyloid-beta peptide (A beta) is generally believed to be a pathological marker of Alzheimer's disease (AD), but it is still of great significance to explore the upstream and downstream relationship of A beta in AD. It is previously reported that c-Abl, a nonreceptor tyrosine kinase, can be activated by A beta, but the interaction between A beta and c-Abl is still unknown. Herein, an extended-gate field-effect transistor (EG-FET)-based sensor has been developed to monitor the level of c-Abl with high sensitivity and selectivity. Our peptide-functionalized EG-FET sensor as the signal transducer can follow c-Abl activity with electron transfer by its specific phosphorylation. The sensor presents a good linear correlation over c-Abl concentrations of 1 pg/mL to 3.05 mu g/mL. The sensor was successfully applied to quantify c-Abl activity in the brain tissue of AD transgenic mice, and the interaction between c-Abl and A beta in AD mice was explored by administering the c-Abl inhibitor (imatinib) and the agonist (DPH). Our work is expected to provide an important reference for early diagnosis and treatment of AD.

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