Fight Aβ Aggregation with Molecular Aggregates

Alzheimer's disease (AD) is the most common form of neurodegenerative disease. Aggregation of amyloid-β peptides (Aβ), a characteristic molecular event of AD, may produce neurotoxic aggregates, notably oligomers that can induce a series of pathogenic change, finally leading to AD. Suppression of Aβ aggregates-induced neurotoxicity via intervention of Aβ aggregation or removal of toxic aggregates are considered as an effective approach for AD treatment. Notably, molecular aggregates formed by assembly of organic molecules have demonstrated promising potential to fight Aβ aggregation due to their advantages, such as high binding affinity, blood-brain barrier permeability, as well as synergistic effect between multiple functionalities, resulting from their unique physicochemical properties in the aggregate state. This review focuses on the recent progress of molecular aggregates for fighting Aβ aggregation in terms of inhibition of Aβ aggregation, redirection of Aβ aggregation into non-toxic aggregates, disassembly of Aβ aggregates, and clearance of Aβ aggregates. Representative examples of the molecular aggregates are categorized by assembly block and manner. Their structural design, working mechanism, and potential of anti-AD are highlighted. Finally, the perspectives and challenges of Aβ aggregation-oriented molecular aggregates for future research are also proposed.