ArticlePloS one2012
ProBDNF collapses neurite outgrowth of primary neurons by activating RhoA.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Brain-Derived Neurotrophic Factor (BDNF) as a Potential Biomarker in Brain Glioma: A Systematic Review and Meta-Analysis.Brain and behavior · 2025Pooled it
- Small molecule modulation of the p75 neurotrophin receptor promotes dendritic spine resilience to pathogenic tau species and reduces their accumulation.Acta neuropathologica communications · 2026Article
- The prognostic potential of circulating BDNF levels and its polymorphisms in age-related cognitive impairment and neurodegeneration.Frontiers in aging neuroscience · 2026Review
- Application of Wuling powder in the treatment of ulcerative colitis complicated by depression as a new therapy principle.World journal of gastroenterology · 2025Article
- Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations.Molecular neurobiology · 2025Review
- Effects of Ninjin'yoeito and physical exercise on serum corticosterone and hippocampal BDNF/proBDNF and neuroinflammation in post-stroke depression in rats.BMC complementary medicine and therapies · 2025Article
- Oxidative Stress Suppresses Trk Signaling While Stimulating JNK-Mediated Endocytosis and Cleavage of p75Journal of neurochemistry · 2025Article
- NgfrNature communications · 2024Article
- Positive Effects of Adiponectin, BDNF, and GLP-1 on Cortical Neurons Counteracting Palmitic Acid Induced Neurotoxicity.Clinical nutrition research · 2024Article
- Elevated Brain-Derived Neurotrophic Factor Levels During Depressive Mixed States.Psychiatry investigation · 2023Article
- Gut Microbiota Taxon-Dependent Transformation of Microglial M1/M2 Phenotypes Underlying Mechanisms of Spatial Learning and Memory Impairment after Chronic Methamphetamine Exposure.Microbiology spectrum · 2023Article
- An Imbalance in the Pro/mature BDNF Ratio Occurs in Multiple Brain Regions During Normal Ageing in Wild-Type Mice.Journal of molecular neuroscience : MN · 2023Article
- ProBDNF and its receptors in immune-mediated inflammatory diseases: novel insights into the regulation of metabolism and mitochondria.Frontiers in immunology · 2023Review
- Aluminium oxide nanoparticles compromise spatial memory performance and proBDNF-mediated neuronal function in the hippocampus of rats.Particle and fibre toxicology · 2022Article
- BDNF and Pro-BDNF in Amyotrophic Lateral Sclerosis: A New Perspective for Biomarkers of Neurodegeneration.Brain sciences · 2022Article
- Brain-derived neurotrophic factor precursor in the immune system is a novel target for treating multiple sclerosis.Theranostics · 2021Article
- Molecular Mechanism for PACAP 38-Induced Neurite Outgrowth in PC12 Cells.Neural plasticity · 2021Article
- Injection of Anti-proBDNF Attenuates Hippocampal-Dependent Learning and Memory Dysfunction in Mice With Sepsis-Associated Encephalopathy.Frontiers in neuroscience · 2021Article
- Requirements of Postnatal proBDNF in the Hippocampus for Spatial Memory Consolidation and Neural Function.Frontiers in cell and developmental biology · 2021Article
- Intervention of Brain-Derived Neurotrophic Factor and Other Neurotrophins in Adult Neurogenesis.Advances in experimental medicine and biology · 2021Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeurons extend their dendrites and axons to build functional neural circuits, which are regulated by both positive and negative signals during development. Brain-derived neurotrophic factor (BDNF) is a positive regulator for neurite outgrowth and neuronal survival but the functions of its precursor (proBDNF) are less characterized. METHODOLOGY/PRINCIPAL
findingsHere we show that proBDNF collapses neurite outgrowth in murine dorsal root ganglion (DRG) neurons and cortical neurons by activating RhoA via the p75 neurotrophin receptor (p75NTR). We demonstrated that the receptor proteins for proBDNF, p75NTR and sortilin, were highly expressed in cultured DRG or cortical neurons. ProBDNF caused a dramatic neurite collapse in a dose-dependent manner and this effect was about 500 fold more potent than myelin-associated glycoprotein. Neutralization of endogenous proBDNF by using antibodies enhanced neurite outgrowth in vitro and in vivo, but this effect was lost in p75NTR(-/-) mice. The neurite outgrowth of cortical neurons from p75NTR deficient (p75NTR(-/-)) mice was insensitive to proBDNF. There was a time-dependent reduction of length and number of filopodia in response to proBDNF which was accompanied with a polarized RhoA activation in growth cones. Moreover, proBDNF treatment of cortical neurons resulted in a time-dependent activation of RhoA but not Cdc42 and the effect was absent in p75NTR(-/-) neurons. Rho kinase (ROCK) and the collapsin response mediator protein-2 (CRMP-2) were also involved in the proBDNF action.
conclusionsproBDNF has an opposing role in neurite outgrowth to that of mature BDNF. Our observations suggest that proBDNF collapses neurites outgrowth and filopodial growth cones by activating RhoA through the p75NTR signaling pathway.
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