Centre for Glycomics, Institute of Chemistry, Slovak Academy of Sciences, Dubravska Cesta 9, SK-84538 Bratislava, Slovakia.
Centre of Excellence for White-Green Biotechnology, Slovak Academy of Sciences, Trieda Andreja Hlinku 2, SK-94976 Nitra, Slovakia.
Int J Mol Sci. 2024 Sep 15;25(18):9961. doi: 10.3390/ijms25189961.
Understanding the pathogenesis and mechanisms of prion diseases can significantly expand our knowledge in the field of neurodegenerative diseases. Prion biology is increasingly recognized as being relevant to the pathophysiology of Alzheimer's disease and Parkinson's disease, both of which affect millions of people each year. This bioinformatics study used a theoretical protein-RNA recognition code (1-L transcription) to reveal the post-transcriptional regulation of the prion protein (PrP). The principle for this method is directly elucidated on PrP, in which an octa-repeat can be 1-L transcribed into a GGA triplet repeat RNA aptamer known to reduce the misfolding of normal PrP into abnormal PrP. The identified genes/proteins are associated with mitochondria, cancer, COVID-19 and ER-stress, and approximately half are directly or indirectly associated with prion diseases. For example, the octa-repeat supports CD44, and regions of the brain with astrocytic prion accumulation also display high levels of CD44.
了解朊病毒疾病的发病机制和机制可以极大地扩展我们在神经退行性疾病领域的知识。朊病毒生物学越来越被认为与阿尔茨海默病和帕金森病的病理生理学有关,这两种疾病每年影响数百万人。这项生物信息学研究使用理论蛋白 RNA 识别码(1-L 转录)来揭示朊病毒蛋白(PrP)的转录后调控。该方法的原理直接在 PrP 上阐明,其中可以将八重复序列 1-L 转录成一个 GGA 三重复 RNA 适体,已知该适体能降低正常 PrP 错误折叠成异常 PrP。鉴定出的基因/蛋白质与线粒体、癌症、COVID-19 和 ER 应激有关,大约一半与朊病毒疾病直接或间接相关。例如,八重复序列支持 CD44,并且具有星形胶质细胞朊病毒积累的大脑区域也显示出高水平的 CD44。