Li Yini, Sun Shuying
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
EMBO J. 2025 Feb;44(3):613-638. doi: 10.1038/s44318-024-00352-6. Epub 2025 Jan 9.
Dysregulation of RNA processing has in recent years emerged as a significant contributor to neurodegeneration. The diverse mechanisms and molecular functions underlying RNA processing underscore the essential role of RNA regulation in maintaining neuronal health and function. RNA molecules are bound by RNA-binding proteins (RBPs), and interactions between RNAs and RBPs are commonly affected in neurodegeneration. In this review, we highlight recent progress in understanding dysregulated RNA-processing pathways and the causes of RBP dysfunction across various neurodegenerative diseases. We discuss both established and emerging mechanisms of RNA-mediated neuropathogenesis in this rapidly evolving field. Furthermore, we explore the development of potential RNA-targeting therapeutic approaches for the treatment of neurodegenerative diseases.
近年来,RNA加工失调已成为神经退行性变的一个重要促成因素。RNA加工背后的多种机制和分子功能突显了RNA调控在维持神经元健康和功能方面的重要作用。RNA分子与RNA结合蛋白(RBP)结合,RNA与RBP之间的相互作用在神经退行性变中通常会受到影响。在这篇综述中,我们重点介绍了在理解各种神经退行性疾病中失调的RNA加工途径以及RBP功能障碍原因方面的最新进展。我们讨论了这个快速发展领域中RNA介导的神经发病机制的既定和新出现的机制。此外,我们还探讨了用于治疗神经退行性疾病的潜在RNA靶向治疗方法的发展。