Amphiphilic Distyrylbenzene Derivatives as Potential Therapeutic and Imaging Agents for Soluble and Insoluble Amyloid β Aggregates in Alzheimer's Disease.

ABSTRACT: Alzheimer's Disease (AD) is the most common neurodegenerative disease, and efficient therapeutic and early diagnostic agents for AD are still lacking. Herein, we report the development of a novel amphiphilic compound, LS-4, generated by linking a hydrophobic amyloid-binding distyrylbenzene fragment with a hydrophilic triazamacrocycle, which dramatically increases the binding affinity toward various amyloid β (Aβ) peptide aggregates, especially for soluble Aβ oligomers. Moreover, upon the administration of LS-4 to 5xFAD mice, fluorescence imaging of LS-4-treated brain sections reveals that LS-4 can penetrate the blood-brain barrier and bind to the Aβ oligomers in vivo. In addition, the treatment of 5xFAD mice with LS-4 reduces the amount of both amyloid plaques and associated phospho

SUBMITTER: Sun L 

PROVIDER: S-EPMC8762579 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature