Abstract
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.
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Acknowledgements
This work is supported by the US National Institutes of Health grants R01NS104041, R01NS125276 and R01MH116220 to S.Z.
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Glossary
- Cryptic exon
-
Unannotated intronic sequences erroneously spliced into mRNA.
- Untranslated regions
-
mRNA regions on each side of a coding sequence that are not translated into protein.
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Nikom, D., Zheng, S. Alternative splicing in neurodegenerative disease and the promise of RNA therapies. Nat. Rev. Neurosci. 24, 457–473 (2023). https://doi.org/10.1038/s41583-023-00717-6
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DOI: https://doi.org/10.1038/s41583-023-00717-6
