Recent developments in the chemical biology of amyloid-β oligomer targeting

Abstract

Aggregation of amyloid-β (Aβ) peptides is characteristic of Alzheimer's disease (AD), which is the most common neurodegenerative disorder. Increasing evidence shows that Aβ oligomers, the intermediates during aggregation, rather than the fully mature fibrils are the most toxic species of Aβ and the key contributors to neurodegeneration. Aβ oligomers have been considered as both biomarkers and drug targets for the diagnosis and treatment of AD. However, the high heterogeneity and metastability of oligomers make it difficult to determine their exact pathogenic mechanisms. Recent developments in Aβ oligomer-targeting agents and techniques have provided great opportunities for overcoming the existing limitations. This review introduces the formation, structure, and toxicity of Aβ oligomers and categorizes the Aβ oligomer-targeting agents based on their chemical biological applications, including recognition and detection of Aβ oligomers for diagnosis, intervention of Aβ oligomerization for treatment, and stabilization of Aβ oligomers for pathogenic studies. The design strategies and working mechanisms of the representative examples published in the past five years are highlighted. Finally, future development directions and challenges of Aβ oligomer targeting are tentatively proposed.