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A β-sheet-targeted theranostic agent for diagnosing and preventing aggregation of pathogenic peptides in Alzheimer’s disease

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Abstract

Amyloid-β peptide (Aβ) aggregates, particularly Aβ oligomers, are established biomarker and toxic species in Alzheimer’s disease (AD). Early detection and disaggregation of Aβ aggregates are of great importance for the treatment of AD due to the unavailability of therapy at the advanced stages of the disease. A multitalented agent, 2-{2-[(1H-benzoimidazol-2-yl)methoxy] phenyl}benzothiazole (BPB), is designed by merging two β-sheet targeting groups into one molecule to detect and inhibit the Aβ aggregation. BPB can quantitatively measure the β-sheet level of soluble Aβ oligomers and specifically distinguish the aggregates of Aβ40 and Aβ42 by unique luminescence spectrum. Animal tests demonstrate that BPB can efficiently penetrate the blood brain barrier and precisely stain Aβ plaques in the brain; more importantly, it can differentiate the blood of APP transgenic mice from that of normal ones. In addition to the diagnostic potential, BPB also suppresses the generation of ROS, protects the neurons from neurotoxicity, and disaggregates the Aβ aggregates in brain homogenates of APP transgenic mice induced by metal ions or self-assembly. In view of its detective ability toward Aβ oligomers and inhibition to Aβ-related neurotoxicity, BPB may be developed into a sensitive probe for screening blood samples in the early diagnosis of AD as well as an effective inhibitor for diminishing Aβ aggregates in the treatment of the disease.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21877059, 31570809, 21731004), the National Basic Research Program of China (2015CB856300), the Natural Science Foundation of Jiangsu Province (BK20150054), and the Research Foundation of the Chinese State Key Laboratory of Coordination Chemistry (SKLCC1912).

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Authors and Affiliations

  1. State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China

    Xiang Ma, Jian Yuan & Zijian Guo

  2. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China

    Tao Yang & Xiaoyong Wang

  3. Model Animal Research Center, Key Laboratory of Model Animal for Disease Study of Ministry of Education, Nanjing University, Nanjing, 210061, China

    Congyu Xu & Guiquan Chen

  4. Chemistry and Chemical Engineering Department, Taiyuan Institute of Technology, Taiyuan, 030008, China

    Xiang Ma & Jiai Hua

  5. School of Chemistry and Chemical Engineering, Yancheng Teachers University, Yancheng, 224002, China

    Yanqing Wang

Authors
  1. Xiang Ma
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  2. Yanqing Wang
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  3. Jiai Hua
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  4. Congyu Xu
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  5. Tao Yang
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  6. Jian Yuan
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  7. Guiquan Chen
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  8. Zijian Guo
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  9. Xiaoyong Wang
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Correspondence to Guiquan Chen, Zijian Guo or Xiaoyong Wang.

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11426_2019_9594_MOESM1_ESM.pdf

A β-Sheet-targeted Theranostic Agent for Diagnosing and Preventing Aggregation of Pathogenic Peptides in Alzheimer’s Disease

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Ma, X., Wang, Y., Hua, J. et al. A β-sheet-targeted theranostic agent for diagnosing and preventing aggregation of pathogenic peptides in Alzheimer’s disease. Sci. China Chem. 63, 73–82 (2020). https://doi.org/10.1007/s11426-019-9594-y

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  • DOI: https://doi.org/10.1007/s11426-019-9594-y

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