ArticleMolecular therapy. Methods & clinical development2015
Silencing p75(NTR) prevents proNGF-induced endothelial cell death and development of acellular capillaries in rat retina.
Article in Molecular therapy. Methods & clinical development, 2015. 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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The trial behind it
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- RNA-seq analysis reveals a positive role for NGF in the myogenic differentiation of bovine skeletal muscle satellite cells.Frontiers in genetics · 2025Article
- The potential role of the p75 receptor in schizophrenia: neuroimmunomodulation and making life or death decisions.Brain, behavior, & immunity - health · 2024Article
- Sortilin Inhibition Protects Neurons From Degeneration in the Diabetic Retina.Investigative ophthalmology & visual science · 2023Article
- Pro Nerve Growth Factor and Its Receptor p75NTR Activate Inflammatory Responses in Synovial Fibroblasts: A Novel Targetable Mechanism in Arthritis.Frontiers in immunology · 2022Article
- In vivo functions of p75Trends in pharmacological sciences · 2021Review
- 2,5-Hexanedione induced apoptosis in rat spinal cord neurons and VSC4.1 cells via the proNGF/p75NTR and JNK pathways.Bioscience reports · 2021Article
- Modulation of p75International journal of molecular sciences · 2021Article
- Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders.Open life sciences · 2021Review
- [Lentivirus-mediated silencing of P75 neurotrophin receptor combined with nerve growth factor overexpression and transfection of bone marrow mesenchymal stem cells combined with demineralized bone matrix for heterotopic osteogenesis].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2020Article
- Article
- Antagonism of proNGF or its receptor p75Diabetologia · 2020Article
- Inactivation of Endothelial ADAM17 Reduces Retinal Ischemia-Reperfusion Induced Neuronal and Vascular Damage.International journal of molecular sciences · 2020Article
- Dexmedetomidine Alleviates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting p75NTR-Mediated Oxidative Stress and Apoptosis.Oxidative medicine and cellular longevity · 2020Article
- Article
- Neuroprotection: Pro-survival and Anti-neurotoxic Mechanisms as Therapeutic Strategies in Neurodegeneration.Frontiers in cellular neuroscience · 2019Review
- Deletion of p75Scientific reports · 2018Article
- High Glucose-Mediated Tyrosine Nitration of PI3-Kinase: A Molecular Switch of Survival and Apoptosis in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2018Article
- Inducible overexpression of endothelial proNGF as a mouse model to study microvascular dysfunction.Biochimica et biophysica acta. Molecular basis of disease · 2018Article
- [Research progress of P75 neurotrophin receptor and new idea of nonunion treatment].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2017Review
- Implication of the neurotrophin receptor p75Expert review of ophthalmology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Accumulation of the nerve growth factor precursor (proNGF) and its receptor p75(NTR) have been associated with several neurodegenerative diseases in both brain and retina. However, whether proNGF contributes to microvascular degeneration remain unexplored. This study seeks to investigate the mechanism by which proNGF/p75(NTR) induce endothelial cell (EC) death and development of acellular capillaries, a surrogate marker of retinal ischemia. Stable overexpression of the cleavage-resistant proNGF and molecular silencing of p75(NTR) were utilized in human retinal EC and rat retinas in vivo. Stable overexpression of proNGF decreased NGF levels and induced retinal vascular cell death evident by 1.9-fold increase in acellular capillaries and activation of JNK and cleaved-PARP that were mitigated by p75(NTR)shRNA. In vitro, overexpression of proNGF did not alter TNF-α level, reduced NGF, however induced EC apoptosis evident by activation of JNK and p38 MAPK, cleaved-PARP. Silencing p75(NTR) using siRNA restored expression of NGF and TrkA activation and prevented EC apoptosis. Treatment of EC with human-mutant proNGF induced apoptosis that coincided with marked protein interaction and nuclear translocation of p75(NTR) and the neurotrophin receptor interacting factor. These effects were abolished by a selective p75(NTR) antagonist. Therefore, targeting p75(NTR) represents a potential therapeutic strategy for diseases associated with aberrant expression of proNGF.
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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.