ArticleActa neuropathologica2021
Huntington's disease brain-derived small RNAs recapitulate associated neuropathology in mice.
Article in Acta neuropathologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Hippocampal small RNAs from patients with schizophrenia induce specific cognitive and neural phenotypes in mice.Cell death discovery · 2026Article
- Mechanisms of Transfer RNA Fragments Functionality Within and Between Cells and Organisms.Cells · 2025Review
- Emerging roles of transfer RNA fragments in the CNS.Brain : a journal of neurology · 2025Review
- Exploring the Potential of tsRNA as Biomarkers for Diagnosis and Treatment of Neurogenetic Disorders.Molecular neurobiology · 2025Review
- Mapping Current Studies of tRNA Fragments onto Disease Landscape.Biomolecules · 2025Review
- Deciphering the role of tRNA-derived fragments in neurological and psychiatric disease pathogenesis.Frontiers in cellular neuroscience · 2025Review
- Small RNAs in plasma extracellular vesicles define biomarkers of premanifest changes in Huntington's disease.Journal of extracellular vesicles · 2024Article
- Advances in the study of the glymphatic system and aging.CNS neuroscience & therapeutics · 2024Review
- [Abnormal transfer RNA epigenetic modifications and related impact on neurodegenerative diseases].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- The length of uninterrupted CAG repeats in stem regions of repeat disease associated hairpins determines the amount of short CAG oligonucleotides that are toxic to cells through RNA interference.Cell death & disease · 2022Article
- tRFs and tRNA Halves: Novel Cellular Defenders in Multiple Biological Processes.Current issues in molecular biology · 2022Review
- Postnatal Conditional Deletion ofBiomedicines · 2022Article
- SPOROS: A pipeline to analyze DISE/6mer seed toxicity.PLoS computational biology · 2022Article
- DISE/6mer seed toxicity-a powerful anti-cancer mechanism with implications for other diseases.Journal of experimental & clinical cancer research : CR · 2021Review
- Oligonucleotides Targeting DNA Repeats DownregulateNucleic acid therapeutics · 2021Article
- Ataxin-2 gene: a powerful modulator of neurological disorders.Current opinion in neurology · 2021Review
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Authors and funding
14 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progressive motor alterations and selective death of striatal medium spiny neurons (MSNs) are key pathological hallmarks of Huntington's disease (HD), a neurodegenerative condition caused by a CAG trinucleotide repeat expansion in the coding region of the huntingtin (HTT) gene. Most research has focused on the pathogenic effects of the resultant protein product(s); however, growing evidence indicates that expanded CAG repeats within mutant HTT mRNA and derived small CAG repeat RNAs (sCAG) participate in HD pathophysiology. The individual contribution of protein versus RNA toxicity to HD pathophysiology remains largely uncharacterized and the role of other classes of small RNAs (sRNA) that are strongly perturbed in HD is uncertain. Here, we demonstrate that sRNA produced in the putamen of HD patients (HD-sRNA-PT) are sufficient to induce HD pathology in vivo. Mice injected with HD-sRNA-PT show motor abnormalities, decreased levels of striatal HD-related proteins, disruption of the indirect pathway, and strong transcriptional abnormalities, paralleling human HD pathology. Importantly, we show that the specific blockage of sCAG mitigates HD-sRNA-PT neurotoxicity only to a limited extent. This observation prompted us to identify other sRNA species enriched in HD putamen with neurotoxic potential. We detected high levels of tRNA fragments (tRFs) in HD putamen, and we validated the neurotoxic potential of an Alanine derived tRF in vitro. These results highlight that HD-sRNA-PT are neurotoxic, and suggest that multiple sRNA species contribute to striatal dysfunction and general transcriptomic changes, favoring therapeutic strategies based on the blockage of sRNA-mediated toxicity.
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