ArticleJCI insight2021
Fidgetin-like 2 negatively regulates axonal growth and can be targeted to promote functional nerve regeneration.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Microtubules in Spinal Cord Injury: From Cytoskeletal Dysregulation to Therapeutic Regeneration.Journal of neurochemistry · 2026Review
- Transcriptomics Insights into Spinal Cord Injury for Therapy Development.International journal of molecular sciences · 2026Review
- Synergy between oral PDE5 inhibitors and topically applied nitric oxide microparticles on the erectile response in a rat model of cavernous nerve injury.International journal of impotence research · 2026Article
- RNA Interference and Its Key Targets for Spinal Cord Injury Therapy: What Is Known So Far?International journal of molecular sciences · 2025Review
- Fidgetin-like 2 knockdown increases acute neuroinflammation and improves recovery in a rat model of spinal cord injury.Journal of neuroinflammation · 2025Article
- Downregulation of Fidgetin-Like 2 Increases Microglial Function: The Relationship Between Microtubules, Morphology, and Activity.Molecular neurobiology · 2025Article
- Nanotechnology in sexual medicine.The journal of sexual medicine · 2024Article
- Nrf2 enhances the therapeutic efficiency of adipose-derived stem cells in the treatment of neurogenic erectile dysfunction in a rat model.Basic and clinical andrology · 2023Article
- Neuro-bone tissue engineering: emerging mechanisms, potential strategies, and current challenges.Bone research · 2023Review
- Fidgetin-like 2 depletion enhances cell migration by regulating GEF-H1, RhoA, and FAK.Biophysical journal · 2023Article
- The Role of Spastin in Axon Biology.Frontiers in cell and developmental biology · 2022Review
- Molecular pathogenesis and treatment of cavernous nerve injury-induced erectile dysfunction: A narrative review.Frontiers in physiology · 2022Review
- Nanotechnology as a tool to advance research and treatment of non-oncologic urogenital diseases.Therapeutic advances in urologyReview
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Authors and funding
10 authors.
Funding
Abstract
The microtubule (MT) cytoskeleton plays a critical role in axon growth and guidance. Here, we identify the MT-severing enzyme fidgetin-like 2 (FL2) as a negative regulator of axon regeneration and a therapeutic target for promoting nerve regeneration after injury. Genetic knockout of FL2 in cultured adult dorsal root ganglion neurons resulted in longer axons and attenuated growth cone retraction in response to inhibitory molecules. Given the axonal growth-promoting effects of FL2 depletion in vitro, we tested whether FL2 could be targeted to promote regeneration in a rodent model of cavernous nerve (CN) injury. The CNs are parasympathetic nerves that regulate blood flow to the penis, which are commonly damaged during radical prostatectomy (RP), resulting in erectile dysfunction (ED). Application of FL2-siRNA after CN injury significantly enhanced functional nerve recovery. Remarkably, following bilateral nerve transection, visible and functional nerve regeneration was observed in 7 out of 8 animals treated with FL2-siRNA, while no control-treated animals exhibited regeneration. These studies identify FL2 as a promising therapeutic target for enhancing regeneration after peripheral nerve injury and for mitigating neurogenic ED after RP - a condition for which, at present, only poor treatment options exist.
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