Neuroscience Graduate Program, University of California, Riverside, Riverside, CA, USA.
Center for RNA Biology and Medicine, University of California, Riverside, Riverside, CA, USA.
Nat Rev Neurosci. 2023 Aug;24(8):457-473. doi: 10.1038/s41583-023-00717-6. Epub 2023 Jun 19.
Alternative splicing generates a myriad of RNA products and protein isoforms of different functions from a single gene. Dysregulated alternative splicing has emerged as a new mechanism broadly implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson disease and repeat expansion diseases. Understanding the mechanisms and functional outcomes of abnormal splicing in neurological disorders is vital in developing effective therapies to treat mis-splicing pathology. In this Review, we discuss emerging research and evidence of the roles of alternative splicing defects in major neurodegenerative diseases and summarize the latest advances in RNA-based therapeutic strategies to target these disorders.
选择性剪接可从单个基因生成具有不同功能的大量 RNA 产物和蛋白质异构体。失调的选择性剪接已成为一种新的机制，广泛涉及阿尔茨海默病、肌萎缩侧索硬化症、额颞叶痴呆、帕金森病和重复扩展疾病等神经退行性疾病的发病机制。了解神经紊乱中异常剪接的机制和功能结果对于开发治疗异常剪接病理的有效疗法至关重要。在这篇综述中，我们讨论了选择性剪接缺陷在主要神经退行性疾病中的作用的新研究和证据，并总结了针对这些疾病的基于 RNA 的治疗策略的最新进展。
