ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Motoneurons secrete angiogenin to induce RNA cleavage in astroglia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 90 citations in OpenAlex.
- Protective role of Angiogenin in muscle regeneration in amyotrophic lateral sclerosis: Diagnostic and therapeutic implications.Brain pathology (Zurich, Switzerland) · 2025Article
- Deciphering the role of tRNA-derived fragments in neurological and psychiatric disease pathogenesis.Frontiers in cellular neuroscience · 2025Review
- Assay for ribosome stimulation of angiogenin nuclease activity.Methods in enzymology · 2025Article
- tsRNAs: A Prospective, Effective Therapeutic Intervention for Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2024Review
- Review
- Article
- RNA: The Unsuspected Conductor in the Orchestra of Macromolecular Crowding.Chemical reviews · 2024Review
- Oxidative Stress, Transfer RNA Metabolism, and Protein Synthesis.Antioxidants & redox signaling · 2024Review
- Quantification of substoichiometric modification reveals global tsRNA hypomodification, preferences for angiogenin-mediated tRNA cleavage, and idiosyncratic epitranscriptomes of human neuronal cell-lines.Computational and structural biotechnology journal · 2023Article
- Protective Effects of Recombinant Human Angiogenin in Keratinocytes: New Insights on Oxidative Stress Response Mediated by RNases.International journal of molecular sciences · 2022Article
- Emerging biological functions of ribonuclease 1 and angiogenin.Critical reviews in biochemistry and molecular biology · 2022Review
- Angiogenin promotes angiogenesis via the endonucleolytic decay of miR-141 in colorectal cancer.Molecular therapy. Nucleic acids · 2022Article
- SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy.Genomics, proteomics & bioinformatics · 2022Article
- Transfer RNA-Derived Fragments and isomiRs Are Novel Components of Chronic TBI-Induced Neuropathology.Biomedicines · 2022Article
- Strengths and Challenges of Secretory Ribonucleases as AntiTumor Agents.Pharmaceutics · 2021Review
- Review
- Angiogenin and tRNA fragments in Parkinson's disease and neurodegeneration.Acta pharmacologica Sinica · 2020Review
- Loss of angiogenin function is related to earlier ALS onset and a paradoxical increase in ALS duration.Scientific reports · 2020Article
- 5'ValCAC tRNA fragment generated as part of a protective angiogenin response provides prognostic value in amyotrophic lateral sclerosis.Brain communications · 2020Article
- Functional roles of the human ribonuclease A superfamily in RNA metabolism and membrane receptor biology.Molecular aspects of medicine · 2019Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder affecting motoneurons. Mutations in angiogenin, encoding a member of the pancreatic RNase A superfamily, segregate with ALS. We previously demonstrated that angiogenin administration shows promise as a neuroprotective therapeutic in studies using transgenic ALS mice and primary motoneuron cultures. Its mechanism of action and target cells in the spinal cord, however, are largely unknown. Using mixed motoneuron cultures, motoneuron-like NSC34 cells, and primary astroglia cultures as model systems, we here demonstrate that angiogenin is a neuronally secreted factor that is endocytosed by astroglia and mediates neuroprotection in paracrine. We show that wild-type angiogenin acts unidirectionally to induce RNA cleavage in astroglia, while the ALS-associated K40I mutant is also secreted and endocytosed, but fails to induce RNA cleavage. Angiogenin uptake into astroglia requires heparan sulfate proteoglycans, and engages clathrin-mediated endocytosis. We show that this uptake mechanism exists for mouse and human angiogenin, and delivers a functional RNase output. Moreover, we identify syndecan 4 as the angiogenin receptor mediating the selective uptake of angiogenin into astroglia. Our data provide new insights into the paracrine activities of angiogenin in the nervous system, and further highlight the critical role of non-neuronal cells in the pathogenesis of ALS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.