Compilation and Analysis of Enzymes, Engineered Antibodies, and Nanoparticles Designed to Interfere with Amyloid-beta Aggregation

The abnormal accumulation and aggregation of amyloid (A) is one of the key factors of the synaptic impairment in Alzheimer's disease. Biomolecules, e.g., apolipoproteins, and membrane receptors, are implicated in the aggregation and toxicity of A. Engineered molecules, such as enzymes, antibodies, and nanoparticles, are designed to interfere with these processes. We compile structural information on these molecules and their essential roles in the complex processes of aggregation, disaggregation, degradation, clearance, and inhibition of A. The interactions between A and its partners have no obvious emerging commonalities. One exception is the recognition of the N-terminal region of A peptides by antibody heavy and light chains, which are facilitated by cooperative interaction not observed in other A-peptide molecules. Overall, the emerging picture charts a diverse, to date unexplored, landscape and serves as the first-of-its-kind partner- and scenario-specific analysis.

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