适体是用于不同靶标的分子识别的通用寡核苷酸配体。然而,到目前为止,适体在淀粉样β蛋白(Aβ)领域的应用受到限制。Aβ是一种内在无序的蛋白质,存在于动态构象平衡中,呈现与时间相关的短命合奏,通常难以分离和表征的亚稳态结构和组件。此外,尽管了解Aβ的潜在生理作用,这种肽与阿尔茨海默病的发病机理有关,其致病作用仍存在争议。迄今为止,积累的科学证据强调了所选适体与不同Aβ组装体之间的不良或非特异性相互作用,这可能是由于Aβ的亚稳态或RNA寡核苷酸对淀粉样蛋白的富含β折叠的纤维结构的固有亲和力。因此,从Aβ-适体研究中得出的教训强调,蛋白质靶标的纯度和均匀性以及适体特异性的严格表征对于实现和获得用于识别Aβ或其他固有无序蛋白质的适体的全部潜能是重要的。这篇综述总结了用于识别不同Aβ组装体的适体研究,并强调了争议,困难,以及此类研究的局限性。
Aptamers are versatile oligonucleotide ligands used for molecular recognition of diverse targets. However, application of aptamers to the field of amyloid β-protein (Aβ) has been limited so far. Aβ 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 Aβ, 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 Aβ assemblies likely due to the metastable nature of Aβ or inherent affinity of RNA oligonucleotides to β-sheet-rich fibrillar structures of amyloidogenic proteins. Accordingly, lessons drawn from Aβ-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 Aβ or other intrinsically disordered proteins. This review summarizes studies of aptamers selected for recognizing different Aβ assemblies and highlights controversies, difficulties, and limitations of such studies.