ArticleNeuron2022
LINE-1 activation in the cerebellum drives ataxia.
Article in Neuron, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Disrupted PQBP1-HNRNPU-LINE-1 axis underlies aberrant neurodevelopment in renpenning syndrome.Molecular psychiatry · 2026Article
- Transposable Elements Are Dynamically Regulated in Medium Spiny Neurons and May Contribute to the Molecular and Behavioral Adaptations to Cocaine.Biological psychiatry · 2026Article
- LINE-1 retrotransposons: Multifaceted functions and regulatory mechanisms in health and disease.Molecular therapy. Nucleic acids · 2026Review
- How somatic evolution affects health.Nature ecology & evolution · 2026Article
- Targeting age-related LINE-1 activation alleviates cardiac aging.Nature aging · 2026Article
- CDK9 Inhibition with enitociclib reveals influence on HERV and LINE RNA abundances in whole blood, T-, and B-Cell lines.BMC medical genomics · 2026Article
- Role of LINE-1 in the nervous system and neurological disorders.Chinese medical journal · 2026Review
- Saliva Spectral Signature and LINE-1 Methylation in Oral Cells: Impact of Air Pollution in São Paulo State Residents.Scientifica · 2026Article
- Repeats mimic pathogen-associated patterns across a vast evolutionary landscape.Cell genomics · 2025Article
- Molecular effects of transposable element sequences in mammalian cells.Genome biology · 2025Review
- Article
- Transposable elements in health and disease: Molecular basis and clinical implications.Chinese medical journal · 2025Review
- Transposable elements as instructors of the immune system.Nature reviews. Immunology · 2025Review
- FUT8 Regulates Cerebellar Neurogenesis and Development Through Maintaining the Level of Neural Cell Adhesion Molecule Cntn2.Molecular neurobiology · 2025Article
- Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.Translational neurodegeneration · 2025Review
- Mitochondria transplantation transiently rescues cerebellar neurodegeneration improving mitochondrial function and reducing mitophagy in mice.Nature communications · 2025Article
- Widespread transposable element dysregulation in human aging brains with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Dynamic dysregulation of retrotransposons in neurodegenerative diseases at the single-cell level.Genome research · 2024Article
- Toll-like receptor 4 deficiency in Purkinje neurons drives cerebellar ataxia by impairing the BK channel-mediated after-hyperpolarization and cytosolic calcium homeostasis.Cell death & disease · 2024Article
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19 authors at 2 institutions in 1 country.
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Abstract
Dysregulation of long interspersed nuclear element 1 (LINE-1, L1), a dominant class of transposable elements in the human genome, has been linked to neurodegenerative diseases, but whether elevated L1 expression is sufficient to cause neurodegeneration has not been directly tested. Here, we show that the cerebellar expression of L1 is significantly elevated in ataxia telangiectasia patients and strongly anti-correlated with the expression of epigenetic silencers. To examine the role of L1 in the disease etiology, we developed an approach for direct targeting of the L1 promoter for overexpression in mice. We demonstrated that L1 activation in the cerebellum led to Purkinje cell dysfunctions and degeneration and was sufficient to cause ataxia. Treatment with a nucleoside reverse transcriptase inhibitor blunted ataxia progression by reducing DNA damage, attenuating gliosis, and reversing deficits of molecular regulators for calcium homeostasis in Purkinje cells. Our study provides the first direct evidence that L1 activation can drive neurodegeneration.
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