title: Inhibition of amyloid-β aggregation in Alzheimer's disease.
abstract: 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.
authors.forename: Qiuming
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.forename: Lingyan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Akron, Akron, Ohio 44325, USA. zhengj@uakron.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000517:prevention & control*; D011485:Protein Binding; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D001688:Biological Products; D010446:Peptide Fragments; D054852:Small Molecule Libraries