ArticleCell death and differentiation2020
Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 87 citations in OpenAlex.
- Retrograde axonal transport of autophagic vesicles and dynein-dynactin protein interaction are attenuated during aging in the rat optic nerve in vivo.Neural regeneration research · 2026Article
- Research progress on the mutual regulatory mechanism of circadian clock genes and autophagy.Frontiers in cell and developmental biology · 2025Review
- AAV-Mediated Expression of miR-17 Enhances Neurite and Axon Regeneration In Vitro.International journal of molecular sciences · 2024Article
- Axonal autophagic vesicle transport in the rat optic nerve in vivo under normal conditions and during acute axonal degeneration.Acta neuropathologica communications · 2024Article
- Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer's disease mice.Journal of translational medicine · 2024Article
- Deletion ofInternational journal of molecular sciences · 2024Article
- Discovery of novel ULK1 inhibitors through machine learning-guided virtual screening and biological evaluation.Future medicinal chemistry · 2024Article
- CaNeural regeneration research · 2023Article
- Protective Effect ofMolecules (Basel, Switzerland) · 2023Article
- Autophagy protein ULK1 interacts with and regulates SARM1 during axonal injury.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Effect of Size and Concentration of Copper Nanoparticles on the Antimicrobial Activity inNanomaterials (Basel, Switzerland) · 2022Article
- Review
- Targeting autophagy in disease: established and new strategies.Autophagy · 2022Article
- The role of autophagic kinases in regulation of axonal function.Frontiers in cellular neuroscience · 2022Review
- RGS6 Drives Spinal Cord Injury by Inhibiting AMPK Pathway in Mice.Disease markers · 2022Article
- Atg7 Knockout Alleviated the Axonal Injury of Neuro-2a Cells Induced by Tri-Ortho-Cresyl Phosphate.Neurotoxicity research · 2021Article
- ULK1 as a novel therapeutic target in neurodegeneration.Neural regeneration research · 2021Article
- Exosomes derived from miR-26a-modified MSCs promote axonal regeneration via the PTEN/AKT/mTOR pathway following spinal cord injury.Stem cell research & therapy · 2021Article
- AAV-mediated inhibition of ULK1 promotes axonal regeneration in the central nervous system in vitro and in vivo.Cell death & disease · 2021Article
- Post-Translational Modifications of the Energy Guardian AMP-Activated Protein Kinase.International journal of molecular sciences · 2021Review
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Axonal degeneration is a key and early pathological feature in traumatic and neurodegenerative disorders of the CNS. Following a focal lesion to axons, extended axonal disintegration by acute axonal degeneration (AAD) occurs within several hours. During AAD, the accumulation of autophagic proteins including Unc-51 like autophagy activating kinase 1 (ULK1) has been demonstrated, but its role is incompletely understood. Here, we study the effect of ULK1 inhibition in different models of lesion-induced axonal degeneration in vitro and in vivo. Overexpression of a dominant negative of ULK1 (ULK1.DN) in primary rat cortical neurons attenuates axotomy-induced AAD in vitro. Both ULK1.DN and the ULK1 inhibitor SBI-0206965 protect against AAD after rat optic nerve crush in vivo. ULK1.DN additionally attenuates long-term axonal degeneration after rat spinal cord injury in vivo. Mechanistically, ULK1.DN decreases autophagy and leads to an mTOR-mediated increase in translational proteins. Consistently, treatment with SBI-0206965 results in enhanced mTOR activation. ULK1.DN additionally modulates the differential splicing of the degeneration-associated genes Kif1b and Ddit3. These findings uncover ULK1 as an important mediator of axonal degeneration in vitro and in vivo, and elucidate its function in splicing, defining it as a putative therapeutic target.
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