Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Instituto de Bioquímica Médica, Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Wiley Interdiscip Rev RNA. 2012 May-Jun;3(3):415-28. doi: 10.1002/wrna.118. Epub 2011 Nov 17.
Prion diseases remain a challenge to modern science in the 21st century because of their capacity for transmission without an encoding nucleic acid. PrP(Sc), the infectious and alternatively folded form of the PrP prion protein, is capable of self-replication, using PrP(C), the properly folded form of PrP, as a template. This process is associated with neuronal death and the clinical manifestation of prion-based diseases. Unfortunately, little is known about the mechanisms that drive this process. Over the last decade, the theory that a nucleic acid, such as an RNA molecule, might be involved in the process of prion structural conversion has become more widely accepted; such a nucleic acid would act as a catalyst rather than encoding genetic information. Significant amounts of data regarding the interactions of PrP with nucleic acids have created a new foundation for understanding prion conversion and the transmission of prion diseases. Our knowledge has been enhanced by the characterization of a large group of RNA molecules known as non-coding RNAs, which execute a series of important cellular functions, from transcriptional regulation to the modulation of neuroplasticity. The RNA-binding properties of PrP along with the competition with other polyanions, such as glycosaminoglycans and nucleic acid aptamers, open new avenues for therapy.
朊病毒疾病在 21 世纪仍然是现代科学的一个挑战，因为它们在没有编码核酸的情况下具有传播能力。PrP（Sc）是 PrP 朊病毒蛋白的传染性和折叠形式，能够自我复制，使用 PrP（C）作为模板，PrP（C）是 PrP 的正确折叠形式。这个过程与神经元死亡和基于朊病毒的疾病的临床表现有关。不幸的是，人们对驱动这个过程的机制知之甚少。在过去的十年中，一种核酸，如 RNA 分子，可能参与朊病毒结构转换过程的理论得到了更广泛的接受；这样的核酸将作为催化剂，而不是编码遗传信息。关于 PrP 与核酸相互作用的大量数据为理解朊病毒转化和朊病毒疾病的传播奠定了新的基础。我们对一大类被称为非编码 RNA 的 RNA 分子的特性有了更深入的了解，这些 RNA 分子执行着一系列重要的细胞功能，从转录调控到神经可塑性的调节。PrP 的 RNA 结合特性以及与其他多阴离子（如糖胺聚糖和核酸适体）的竞争为治疗开辟了新的途径。
