Inhibition of Amyloid-β Aggregation in Alzheimer's Disease
The assembly of naturally occurring amyloid peptides into cytotoxic oligomeric and fibrillar aggregates is believed to be a major
pathologic event in over 25 human diseases. Blocking of or interfering with the aggregation of amyloid peptides such as amyloid-β
(Aβ) using small organic molecules, peptides and peptidomimetics, and nanoparticles that selectively bind or inhibit Aβ aggregates is a
promising strategy for the development of novel pharmaceutical approaches and agents to treat Alzheimer's disease (AD). In a broad
sense, considering many common features in structure, kinetics, and biological activity of amyloid peptides, potent inhibitors and associated
inhibition strategies that are developed for targeting Aβ aggregation could also be generally applied to other amyloid-forming peptides
in “protein-aggregation diseases”. Due to the complex nature of Aβ self-assembly process, increasing knowledge in high-resolution
structures of Aβ oligomers, atomic-level Aβ-inhibitor binding information, and cost-effective high-throughput screening method will improve
our fundamental understanding of amyloid formation and inhibition mechanisms, as well as practical design of pharmaceutical
strategies and drugs to treat AD. This review summarizes major findings, recent advances, and future challenges for the development of
new Aβ-aggregation inhibitors, mainly focusing on three major classes of Aβ inhibitors with associated inhibition mechanisms and practical examples.
Keywords: Amyloid-beta, Amyloid inhibitor, Amyloid toxicity, Protein aggregation, Alzheimer disease.
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