Aptamers Selected for Recognizing Amyloid beta-Protein-A Case for Cautious Optimism

Abstract

Aptamers are versatile oligonucleotide ligands used for molecular recognition of diverse targets. However, application of aptamers to the field of amyloid beta-protein (A beta) has been limited so far. A beta is an intrinsically disordered protein that exists in a dynamic conformational equilibrium, presenting time-dependent ensembles of short-lived, metastable structures and assemblies that have been generally difficult to isolate and characterize. Moreover, despite understanding of potential physiological roles of A beta, this peptide has been linked to the pathogenesis of Alzheimer disease, and its pathogenic roles remain controversial. Accumulated scientific evidence thus far highlights undesirable or nonspecific interactions between selected aptamers and different A beta assemblies likely due to the metastable nature of A beta or inherent affinity of RNA oligonucleotides to beta-sheet-rich fibrillar structures of amyloidogenic proteins. Accordingly, lessons drawn from A beta-aptamer studies emphasize that purity and uniformity of the protein target and rigorous characterization of aptamers' specificity are important for realizing and garnering the full potential of aptamers selected for recognizing A beta or other intrinsically disordered proteins. This review summarizes studies of aptamers selected for recognizing different A beta assemblies and highlights controversies, difficulties, and limitations of such studies.