Development of novel theranostic agents for in vivo amyloid imaging and protective effects on human neuroblastoma cells.

Abstract

Brain amyloid deposits have been identified as the main neuropathological hallmarks of Alzheimer's diseases (AD) and intensive efforts have been devoted to develop aggregation inhibitors preventing the formation of toxic oligomeric Aβ for therapeutic. In addition, evidence indicates that the formation and accumulation of β-amyloid plaques probably precede clinical symptoms by around 20 years and imaging of such plaques would be beneficial for early-stage AD detection. In this study, we investigated phenothiazine-based compounds as novel promising theranostic agents for AD. These multifunctional agents exhibited BBB permeability, low neurotoxicity, good bio-stability as well as strong turn-on fluorescence with a Stokes shift upon binding to Aβ aggregates. They had metal-chelating property which could delay Aβ aggregation and displayed high binding affinity for β-amyloid aggregates. Moreover, they have been simultaneously applied to perform in vivo near-infrared fluorescence imaging of β-amyloid plaques in double transgenic AD mouse model, to prevent self-aggregation of Aβ monomer from forming toxic oligomers and to protect human neuroblastoma SH-SY5Y cells against Aβ-induced toxicity and oxidative stress.

• Authors: Yongliang Li, Longjia Yan, Jing Cai, Wanzheng Zhang, Li Li, Zhiyun Du, Changzhi Dong, Bernard Meunier, Huixiong Chen
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 181 Pg. 111585 (Nov 01 2019) ISSN: 1768-3254 [Electronic] France
• PMID: 31404860 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Neuroprotective Agents
• Phenothiazines
• phenothiazine

Topics

• Alzheimer Disease (diagnostic imaging, drug therapy, metabolism)
• Amyloid beta-Peptides (analysis, metabolism)
• Animals
• Cell Line, Tumor
• Humans
• Male
• Mice, Inbred C57BL
• Mice, Transgenic
• Neuroprotective Agents (chemistry, pharmacokinetics, therapeutic use)
• Optical Imaging
• Phenothiazines (chemistry, pharmacokinetics, therapeutic use)
• Plaque, Amyloid (diagnostic imaging, drug therapy)
• Protein Aggregation, Pathological (diagnostic imaging, metabolism, prevention & control)
• Theranostic Nanomedicine