ArticlePloS one2015
Functional Characterization of Human ProNGF and NGF Mutants: Identification of NGF P61SR100E as a "Painless" Lead Investigational Candidate for Therapeutic Applications.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- CHF6467 Exerts Neuroprotective Effects in the Rat Model of Acute Ischemic Stroke.Brain sciences · 2026Article
- Simultaneous Electrochemical Detection of NGF and proNGF Under Native Conditions Using Molecularly Imprinted Polymers: Toward Point-of-Care Diagnosis of Alzheimer's Disease.Advanced healthcare materials · 2026Article
- Toward an NGF-based therapy for Rett syndrome.Frontiers in neuroscience · 2026Review
- Chemical Synthesis and Chaperone Peptide Mediated Folding of Human Nerve Growth Factor by Expressed KAHA Ligation.ACS central science · 2025Article
- Article
- Development and Characterization of a Photocrosslinkable, Chitosan-Based, Nerve Growth Factor-Eluting Hydrogel for the Ocular Surface.Translational vision science & technology · 2024Article
- Reversal of neurological deficits by painless nerve growth factor in a mouse model of Rett syndrome.Brain : a journal of neurology · 2024Article
- Role of ATP in migraine mechanisms: focus on P2X3 receptors.The journal of headache and pain · 2023Review
- Cerebrospinal fluid level of proNGF as potential diagnostic biomarker in patients with frontotemporal dementia.Frontiers in aging neuroscience · 2023Article
- Encapsulation of β-NGF in injectable microrods for localized delivery accelerates endochondral fracture repair.Frontiers in bioengineering and biotechnology · 2023Article
- Nerve growth factor promotes differentiation and protects the oligodendrocyte precursor cells fromFrontiers in neuroscience · 2023Article
- Neurotrophic Activity and Its Modulation by Zinc Ion of a Dimeric Peptide Mimicking the Brain-Derived Neurotrophic Factor N-Terminal Region.ACS chemical neuroscience · 2022Article
- Getting Into the Brain: The Intranasal Approach to Enhance the Delivery of Nerve Growth Factor and Its Painless Derivative in Alzheimer's Disease and Down Syndrome.Frontiers in neuroscience · 2022Article
- The effects of painless nerve growth factor on human microglia polarization.Frontiers in cellular neuroscience · 2022Article
- Oligodendrocyte precursor cell maturation: role of adenosine receptors.Neural regeneration research · 2021Review
- Nerve Growth Factor Neutralization Promotes Oligodendrogenesis by Increasing miR-219a-5p Levels.Cells · 2021Article
- proNGF Measurement in Cerebrospinal Fluid Samples of a Large Cohort of Living Patients With Alzheimer's Disease by a New Automated Immunoassay.Frontiers in aging neuroscience · 2021Article
- Nerve Growth Factor-Based Therapy in Alzheimer's Disease and Age-Related Macular Degeneration.Frontiers in neuroscience · 2021Review
- AFrontiers in neuroscience · 2021Review
- NT3Stem cell research & therapy · 2019Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNerve Growth Factor (NGF) holds a great therapeutic promise for Alzheimer's disease, diabetic neuropathies, ophthalmic diseases, dermatological ulcers. However, the necessity for systemic delivery has hampered the clinical applications of NGF due to its potent pro-nociceptive action. A "painless" human NGF (hNGF R100E) mutant has been engineered. It has equal neurotrophic potency to hNGF but a lower nociceptive activity. We previously described and characterized the neurotrophic and nociceptive properties also of the hNGF P61S and P61SR100E mutants, selectively detectable against wild type hNGF. However, the reduced pain-sensitizing potency of the "painless" hNGF mutants has not been quantified. OBJECTIVES AND
resultsAiming at the therapeutic application of the "painless" hNGF mutants, we report on the comparative functional characterization of the precursor and mature forms of the mutants hNGF R100E and hNGF P61SR100E as therapeutic candidates, also in comparison to wild type hNGF and to hNGF P61S. The mutants were assessed by a number of biochemical, biophysical methods and assayed by cellular assays. Moreover, a highly sensitive ELISA for the detection of the P61S-tagged mutants in biological samples has been developed. Finally, we explored the pro-nociceptive effects elicited by hNGF mutants in vivo, demonstrating an expanded therapeutic window with a ten-fold increase in potency.
conclusionsThis structure-activity relationship study has led to validate the concept of developing painless NGF as a therapeutic, targeting the NGF receptor system and supporting the choice of hNGF P61S R100E as the best candidate to advance in clinical development. Moreover, this study contributes to the identification of the molecular determinants modulating the properties of the hNGF "painless" mutants.
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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.