ArticleThe Journal of clinical investigation2018
Role of proNGF/p75 signaling in bladder dysfunction after spinal cord injury.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Taming the "death receptor": translating the first-in-class p75Journal of translational medicine · 2026Review
- Serotonergic System-Targeted Nucleic Acid Hydrogel Coordinates Excitability Restoration and Circuit Reconstruction for Spinal Cord Injury Therapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Intravesical instillation of pirfenidone/polydopamine nanoparticles for managing neurogenic bladder post-spinal cord injury by alleviating bladder inflammation and fibrosis.Journal of nanobiotechnology · 2026Article
- Spinal cord injury-induced overflow incontinence reshapes the activin-follistatin-inhibin axis in mouse bladder and kidney.Frontiers in molecular biosciences · 2026Article
- Inhibition of CSPG-PTPσ Activates Autophagy Flux and Lysosome Fusion, Aids Axon and Synaptic Reorganization in Spinal Cord Injury.Molecular neurobiology · 2025Article
- Progression of mesenchymal stem cell regulation on imbalanced microenvironment after spinal cord injury.Stem cell research & therapy · 2024Review
- Axonal growth inhibitors and their receptors in spinal cord injury: from biology to clinical translation.Neural regeneration research · 2023Review
- Targeting neurotrophin and nitric oxide signaling to promote recovery and ameliorate neurogenic bladder dysfunction following spinal cord injury - Mechanistic concepts and clinical implications.Continence (Amsterdam, Netherlands) · 2023Article
- Molecular Mechanisms of Neurogenic Lower Urinary Tract Dysfunction after Spinal Cord Injury.International journal of molecular sciences · 2023Review
- Changes in nerve growth factor signaling in female mice with cyclophosphamide-induced cystitis.Frontiers in urology · 2023Article
- Acetyl-11-keto-beta-boswellic acid promotes sciatic nerve repair after injury: molecular mechanism.Neural regeneration research · 2022Article
- Article
- Nerve growth factor-mediated NaLife sciences · 2022Article
- Targeting neurotrophin and nitric oxide signaling to treat spinal cord injury and associated neurogenic bladder overactivity.Continence (Amsterdam, Netherlands) · 2022Article
- Biomarkers from Secondary Complications in Spinal Cord Injury.Current pharmacology reports · 2022Article
- Effects of pharmacological neurotrophin receptor inhibition on bladder function in female mice with cyclophosphamide-induced cystitis.Frontiers in urology · 2022Article
- In vivo functions of p75Trends in pharmacological sciences · 2021Review
- Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity.Scientific reports · 2021Article
- Imbalance of nerve growth factor metabolism in aging women with overactive bladder syndrome.World journal of urology · 2021Article
- Small molecule modulation of the p75 neurotrophin receptor suppresses age- and genotype-associated neurodegeneration in HIV gp120 transgenic mice.Experimental neurology · 2021Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Loss of bladder control is a challenging outcome facing patients with spinal cord injury (SCI). We report that systemic blocking of pro-nerve growth factor (proNGF) signaling through p75 with a CNS-penetrating small-molecule p75 inhibitor resulted in significant improvement in bladder function after SCI in rodents. The usual hyperreflexia was attenuated with normal bladder pressure, and automatic micturition was acquired weeks earlier than in the controls. The improvement was associated with increased excitatory input to the spinal cord, in particular onto the tyrosine hydroxylase-positive fibers in the dorsal commissure. The drug also had an effect on the bladder itself, as the urothelial hyperplasia and detrusor hypertrophy that accompany SCI were largely prevented. Urothelial cell loss that precedes hyperplasia was dependent on p75 in response to urinary proNGF that is detected after SCI in rodents and humans. Surprisingly, death of urothelial cells and the ensuing hyperplastic response were beneficial to functional recovery. Deleting p75 from the urothelium prevented urothelial death, but resulted in reduction in overall voiding efficiency after SCI. These results unveil a dual role of proNGF/p75 signaling in bladder function under pathological conditions with a CNS effect overriding the peripheral one.
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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.