Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar, Hyderabad, Telangana, 500037, India.
Cell Mol Neurobiol. 2022 Oct;42(7):2075-2095. doi: 10.1007/s10571-021-01093-4. Epub 2021 May 1.
Exploring the microRNAs and aptamers for their therapeutic role as biological drugs has expanded the horizon of its applicability against various human diseases, explicitly targeting the genetic materials. RNA-based therapeutics are widely being explored for the treatment and diagnosis of multiple diseases, including neurodegenerative disorders (NDD). Latter includes microRNA, aptamers, ribozymes, and small interfering RNAs (siRNAs), which control the gene expression mainly at the transcriptional strata. One RNA transcript translates into different protein types; hence, therapies targeted at the transcriptional sphere may have prominent and more extensive effects than alternative therapeutics. Unlike conventional gene therapy, RNAs, upon delivery, can either altogether abolish or alter the synthesis of the protein of interest, therefore, regulating their activities in a controlled and diverse manner. NDDs like Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, Prion disease, and others are characterized by deposition of misfolded protein such as amyloid-ß, tau, α-synuclein, huntingtin and prion proteins. Neuroinflammation, one of the perquisites for neurodegeneration, is induced during neurodegenerative pathogenesis. In this review, we discuss microRNAs and aptamers' role as two different RNA-based approaches for their unique ability to regulate protein production at the transcription level, hence offering many advantages over other biologicals. The microRNA acts either by alleviating the malfunctioning RNA expression or by working as a replacement to lost microRNA. On the contrary, aptamer act as a chemical antibody and forms an aptamer-target complex.
探索 microRNA 和适体作为生物药物的治疗作用,扩展了其针对各种人类疾病的适用性,明确针对遗传物质。基于 RNA 的疗法广泛用于治疗和诊断多种疾病,包括神经退行性疾病 (NDD)。后者包括 microRNA、适体、核酶和小干扰 RNA (siRNA),它们主要在转录层控制基因表达。一个 RNA 转录本翻译成不同的蛋白质类型;因此,靶向转录域的疗法可能比替代疗法具有更显著和更广泛的效果。与传统的基因治疗不同,RNA 在递送至细胞后可以完全消除或改变靶蛋白的合成,因此可以以受控和多样化的方式调节它们的活性。阿尔茨海默病、帕金森病、亨廷顿病、多发性硬化症、朊病毒病等神经退行性疾病的特征是错误折叠的蛋白质如淀粉样蛋白-β、tau、α-突触核蛋白、亨廷顿蛋白和朊病毒蛋白的沉积。神经炎症是神经退行性发病机制中神经变性的一个先决条件。在这篇综述中,我们讨论了 microRNA 和适体作为两种不同的基于 RNA 的方法的作用,因为它们具有独特的能力,可以在转录水平调节蛋白质的产生,因此优于其他生物制剂。microRNA 可以通过减轻功能失调的 RNA 表达或作为丢失的 microRNA 的替代品来发挥作用。相反,适体作为化学抗体起作用,并形成适体-靶复合物。