Revealing the amyloid β-protein with zinc finger protein of micronucleus during Alzheimer's disease progress by a quaternary ammonium terpyridine probe

Haitao Ding; Shangke Liu; Wei Du; Liping Su; Junyang Chen; Yupeng Tian; Dayi Pan; Lei Chen; Loris Rizzello; Xiaowei Zheng; Giuseppe Battaglia; Kui Luo; Qiyong Gong; Xiaohe Tian

doi:10.1016/j.bios.2023.115446

Revealing the amyloid β-protein with zinc finger protein of micronucleus during Alzheimer's disease progress by a quaternary ammonium terpyridine probe

Biosens Bioelectron. 2023 Sep 15:236:115446. doi: 10.1016/j.bios.2023.115446. Epub 2023 Jun 3.

Authors

Haitao Ding¹, Shangke Liu², Wei Du³, Liping Su¹, Junyang Chen⁴, Yupeng Tian⁵, Dayi Pan¹, Lei Chen⁶, Loris Rizzello⁷, Xiaowei Zheng⁸, Giuseppe Battaglia⁴, Kui Luo⁹, Qiyong Gong¹⁰, Xiaohe Tian¹¹

Affiliations

¹ Department of Radiology and National Clinical Research Center for Geriatrics, Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province; Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610000, Sichuan Province, China.
² Department of Dermatology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
³ School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China. Electronic address: duwei1247@163.com.
⁴ Department of Chemistry, University College London, London, United Kingdom.
⁵ Department of Chemistry, Key Laboratory of Functional Inorganic Material Chemistry of Anhui Province, Hefei, 230039, China.
⁶ Department of Chemistry, Key Laboratory of Functional Inorganic Material Chemistry of Anhui Province, Hefei, 230039, China. Electronic address: chenlei@wchscu.cn.
⁷ Department of Pharmaceutical Sciences - University of Milan, Via G. Balzaretti 9, 20133, Milan, IT, Italy; The National Institute of Molecular Genetics (INGM), Via Francesco Sforza 35, 20122, Milan, IT, Italy.
⁸ Department of Endocrinology and Metabolism, Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, China; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁹ Department of Radiology and National Clinical Research Center for Geriatrics, Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province; Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610000, Sichuan Province, China; Functional and Molecular Imaging Key Laboratory of Sichuan Province, And Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China.
¹⁰ Department of Radiology and National Clinical Research Center for Geriatrics, Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province; Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610000, Sichuan Province, China; Functional and Molecular Imaging Key Laboratory of Sichuan Province, And Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China; Department of Radiology, West China Xiamen Hospital of Sichuan University, 699 Jinyuan Xi Road, Jimei District, 361021, Xiamen, Fujian, China.
¹¹ Department of Radiology and National Clinical Research Center for Geriatrics, Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province; Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610000, Sichuan Province, China. Electronic address: xiaohe.t@wchscu.cn.

PMID: 37290288
DOI: 10.1016/j.bios.2023.115446

Abstract

Micronucleus (MN) is regarded as an abnormal structure in eukaryotic cells which can be used as a biomarker for genetic instability. However, direct observation of MN in living cells is rarely achieved due to the lack of probes that are capable of distinguishing nuclear- and MN-DNA. Herein, a water-soluble terpyridine organic small molecule (ABT) was designed and employed to recognize Zinc-finger protein (ZF) for imaging intracellular MN. The in vitro experiments suggested ABT has a high affinity towards ZF. Further live cell staining showed that ABT could selectively target MN in HeLa and NSC34 cells when combined with ZF. Importantly, we use ABT to uncover the correlation between neurotoxic amyloid β-protein (Aβ) and MN during Alzheimer's disease (AD) progression. Thus, this study provides profound insight into the relationship between Aβ and genomic disorders, offering a deeper understanding for the diagnosis and treatment of AD.

Keywords: Alzheimer's disease; Amyloid β-protein; Bioimaging; Micronuclei; Zinc finger protein.

MeSH terms

Alzheimer Disease* / diagnosis
Alzheimer Disease* / metabolism
Amyloid beta-Peptides / chemistry
Biosensing Techniques*
HeLa Cells
Humans

Substances

Amyloid beta-Peptides