ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Defective cAMP generation underlies the sensitivity of CNS neurons to neurofibromatosis-1 heterozygosity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 109 citations in OpenAlex.
- Retinal changes in neurofibromatosis type 1 patients without optic pathway glioma: A systematic review and meta-analysis of optical coherence tomography findings.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Genetic and non-genetic factors influencing phenotypic variability in neurofibromatosis type 1.Orphanet journal of rare diseases · 2026Review
- Inhibition of Cxcr4 chemokine receptor signaling improves habituation learning in a zebrafish model of neurofibromatosis.Disease models & mechanisms · 2026Article
- Review
- Genetics and current research models of Mendelian tumor predisposition syndromes with ocular involvement.Progress in retinal and eye research · 2025Review
- Inner retinal layer thickness alterations in adult and pediatric patients with neurofibromatosis 1.Scientific reports · 2024Article
- Neurofibromin deficiency alters the patterning and prioritization of motor behaviors in a state-dependent manner.bioRxiv : the preprint server for biology · 2024Article
- An Overview of Optic Pathway Glioma With Neurofibromatosis Type 1: Pathogenesis, Risk Factors, and Therapeutic Strategies.Investigative ophthalmology & visual science · 2024Review
- Review
- Estrogen-induced glial IL-1β mediates extrinsic retinal ganglion cell vulnerability in murine Nf1 optic glioma.Annals of clinical and translational neurology · 2024Article
- Interactions between Ras and Rap signaling pathways during neurodevelopment in health and disease.Frontiers in molecular neuroscience · 2024Review
- Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium.Molecular neurodegeneration · 2023Review
- The therapeutic potential of neurofibromin signaling pathways and binding partners.Communications biology · 2023Review
- Neurofibromatosis Type 1-Associated Optic Pathway Gliomas: Current Challenges and Future Prospects.Cancer management and research · 2023Review
- Mechanistic insights from animal models of neurofibromatosis type 1 cognitive impairment.Disease models & mechanisms · 2022Review
- Review
- RAS and beyond: the many faces of the neurofibromatosis type 1 protein.Disease models & mechanisms · 2022Article
- Regulation of HCN Channels by Protein Interactions.Frontiers in physiology · 2022Review
- Neuroretinal dysfunction in patients affected by neurofibromatosis type 1.International journal of ophthalmology · 2022Article
- Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila.Nature communications · 2021Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Individuals with the neurofibromatosis type 1 (NF1) inherited cancer syndrome exhibit neuronal dysfunction that predominantly affects the CNS. In this report, we demonstrate a unique vulnerability of CNS neurons, but not peripheral nervous system (PNS) neurons, to reduced Nf1 gene expression. Unlike dorsal root ganglion neurons, Nf1 heterozygous (Nf1+/-) hippocampal and retinal ganglion cell (RGC) neurons have decreased growth cone areas and neurite lengths, and increased apoptosis compared to their wild-type counterparts. These abnormal Nf1+/- CNS neuronal phenotypes do not reflect Ras pathway hyperactivation, but rather result from impaired neurofibromin-mediated cAMP generation. In this regard, elevating cAMP levels with forskolin or rolipram treatment, but not MEK (MAP kinase kinase) or PI3-K (phosphatidylinositol 3-kinase) inhibition, reverses these abnormalities to wild-type levels in vitro. In addition, Nf1+/- CNS, but not PNS, neurons exhibit increased apoptosis in response to excitotoxic or oxidative stress in vitro. Since children with NF1-associated optic gliomas often develop visual loss and Nf1 genetically engineered mice with optic glioma exhibit RGC neuronal apoptosis in vivo, we further demonstrate that RGC apoptosis resulting from optic glioma in Nf1 genetically engineered mice is attenuated by rolipram treatment in vivo. Similar to optic glioma-induced RGC apoptosis, the increased RGC neuronal death in Nf1+/- mice after optic nerve crush injury is also attenuated by rolipram treatment in vivo. Together, these findings establish a distinctive role for neurofibromin in CNS neurons with respect to vulnerability to injury, define a CNS-specific neurofibromin intracellular signaling pathway responsible for neuronal survival, and lay the foundation for future neuroprotective glioma treatment approaches.
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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.