Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, USA.
Center for Innovation in Brain Science, Tucson, Arizona, USA.
Nucleic Acid Ther. 2022 Aug;32(4):235-250. doi: 10.1089/nat.2021.0091. Epub 2022 Apr 22.
Neurodegeneration is a progressive deterioration of neural structures leading to cognitive or motor impairment of the affected patient. There is still no effective therapy for any of the most common neurodegenerative diseases (NDs) such as Alzheimer's or Parkinson's disease. Although NDs exhibit distinct clinical characteristics, many are characterized by the accumulation of misfolded proteins or peptide fragments in the brain and/or spinal cord. The presence of similar inclusion bodies in patients with diverse NDs provides a rationale for developing therapies directed at overlapping disease mechanisms. A novel targeting strategy involves the use of aptamers for therapeutic development. Aptamers are short nucleic acid ligands able to recognize molecular targets with high specificity and high affinity. Despite the fact that several academic groups have shown that aptamers have the potential to be used in therapeutic and diagnostic applications, their clinical translation is still limited. In this study, we describe aptamers that have been developed against proteins relevant to NDs, including prion protein and amyloid beta (Aβ), cell surface receptors and other cytoplasmic proteins. This review also describes advances in the application of these aptamers in imaging, protein detection, and protein quantification, and it provides insights about their accelerated clinical use for disease diagnosis and therapy.
神经退行性变是指神经结构的进行性恶化,导致受影响患者的认知或运动功能受损。目前,对于阿尔茨海默病或帕金森病等最常见的神经退行性疾病(NDs),仍没有有效的治疗方法。尽管 NDs 表现出不同的临床特征,但许多疾病的特征是脑和/或脊髓中错误折叠的蛋白质或肽片段的积累。不同 NDs 患者中存在相似的包涵体为开发针对重叠疾病机制的治疗方法提供了依据。一种新的靶向策略涉及使用适体进行治疗开发。适体是能够高度特异性和高亲和力识别分子靶标的短核酸配体。尽管有几个学术团体已经表明适体具有在治疗和诊断应用中的潜力,但它们的临床转化仍然有限。在这项研究中,我们描述了针对与 NDs 相关的蛋白质(包括朊病毒蛋白和淀粉样β(Aβ)、细胞表面受体和其他细胞质蛋白)开发的适体。这篇综述还描述了这些适体在成像、蛋白质检测和蛋白质定量中的应用进展,并提供了有关它们在疾病诊断和治疗中的加速临床应用的见解。