Cordeiro Yraima, Macedo Bruno, Silva Jerson L, Gomes Mariana P B
Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
Cidade Universitária, Av. Carlos Chagas Filho 373, Prédio do CCS, Bloco B, Subsolo, Sala 17, Rio de Janeiro, RJ, 21941-902, Brazil.
Biophys Rev. 2014 Mar;6(1):97-110. doi: 10.1007/s12551-013-0132-0. Epub 2014 Jan 9.
Protein misfolding disorders (PMDs) refer to a group of diseases related to the misfolding of particular proteins that aggregate and deposit in the cells and tissues of humans and other mammals. The mechanisms that trigger protein misfolding and aggregation are still not fully understood. Increasing experimental evidence indicates that abnormal interactions between PMD-related proteins and nucleic acids (NAs) can induce conformational changes. Here, we discuss these protein-NA interactions and address the role of deoxyribonucleic (DNA) and ribonucleic (RNA) acid molecules in the conformational conversion of different proteins that aggregate in PMDs, such as Alzheimer's, Parkinson's, and prion diseases. Studies on the affinity, stability, and specificity of proteins involved in neurodegenerative diseases and NAs are specifically addressed. A landscape of reciprocal effects resulting from the binding of prion proteins, amyloid-β peptides, tau proteins, huntingtin, and α-synuclein are presented here to clarify the possible role of NAs, not only as encoders of genetic information but also in triggering PMDs.
蛋白质错误折叠疾病（PMDs）是指与特定蛋白质错误折叠相关的一组疾病，这些蛋白质在人类和其他哺乳动物的细胞和组织中聚集并沉积。引发蛋白质错误折叠和聚集的机制仍未完全了解。越来越多的实验证据表明，PMD相关蛋白质与核酸（NAs）之间的异常相互作用可诱导构象变化。在此，我们讨论这些蛋白质-NA相互作用，并阐述脱氧核糖核酸（DNA）和核糖核酸（RNA）分子在不同蛋白质构象转换中的作用，这些蛋白质在PMDs中聚集，如阿尔茨海默病、帕金森病和朊病毒病。特别讨论了对神经退行性疾病中涉及的蛋白质与NAs的亲和力、稳定性和特异性的研究。本文展示了朊病毒蛋白、淀粉样β肽、tau蛋白、亨廷顿蛋白和α-突触核蛋白结合产生的相互作用图景，以阐明NAs的可能作用，NAs不仅作为遗传信息的编码者，还在引发PMDs中发挥作用。
