Figure 3.

Schematic representation of the generic strategy for search of peptide-based therapeutic agents affecting Aβ production pathways and/or suppressing neurotoxic effects of Aβ oligomers. The therapeutic agent (shown in red) can (1) act at the stage of APP processing through interaction with Aβ precursors (in green) processed by γ-secretase complex (PDB: 6IYC), modifying production of mature Aβ isoforms; (2) bind soluble Aβ aggregates, suppressing their toxicity; (3) interfere with interactions of toxic Aβ aggregates with membrane surface, inhibiting their conversion into β-structured membrane-bound oligomers; (4) modify toxic properties of membrane-incorporated Aβ oligomers associated with membrane permeabilization [140]; (5) target pore-like transmembrane structures formed by Aβ oligomers (PDB: 6RHY), e.g., inhibiting transmembrane transport of cations; and (6) prevent Aβ from inducing abnormal functioning of soluble and membrane-associated proteins, e.g., nicotinic acetylcholine receptor (PDB: 2BG9), which can be inhibited by diverse Aβ oligomers in different manners.