ArticleCell death and differentiation2013
ProNGF\NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Postmortem Brain, Cerebrospinal Fluid, and Blood Neurotrophic Factor Levels in Alzheimer's Disease: A Systematic Review and Meta-Analysis.Journal of molecular neuroscience : MN · 2018Pooled it
- p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial.Nature medicine · 2024Trial
- Nerve growth factor receptor (NGFR): A key player in glioblastoma progression.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- 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
- Modulatory Role of Arbutin on Hepatic Inflammation and Apoptosis After Mild Repetitive Traumatic Brain Injury in Experimental Rats: Involvement of NGF/TrkA and IL-6/JAK2/STAT3 Immune Signaling Crosstalk.Biochemistry research international · 2026Article
- A neurotrophic withdrawal hypothesis for multisystem adverse events associated with anti-NGF therapy for canine osteoarthritis pain.Frontiers in veterinary science · 2026Article
- Application of Neurotrophic Factors as a Therapeutic Approach for Neurodegenerative Diseases.Experimental neurobiology · 2025Review
- Delivery of Neuroregenerative Proteins to the Brain for Treatments of Neurodegenerative Brain Diseases.Life (Basel, Switzerland) · 2024Review
- FNDC5/irisin mediates the protective effects of Innovative theta-shaking exercise on mouse memory.Heliyon · 2024Article
- Surfeit Locus Protein 4 as a Novel Target for Therapeutic Intervention in Cerebral Ischemia-Reperfusion Injury.Molecular neurobiology · 2024Article
- Enhancement of neural regeneration as a therapeutic strategy for Alzheimer's disease (Review).Experimental and therapeutic medicine · 2023Review
- Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer's Disease Mice.Journal of molecular neuroscience : MN · 2023Article
- Neurotrophic factor-based pharmacological approaches in neurological disorders.Neural regeneration research · 2023Review
- Glia-Neurotrophic Factor Relationships: Possible Role in Pathobiology of Neuroinflammation-Related Brain Disorders.International journal of molecular sciences · 2023Review
- Building better brains: the pleiotropic function of neurotrophic factors in postnatal cerebellar development.Frontiers in molecular neuroscience · 2023Review
- Cerebrospinal fluid level of proNGF as potential diagnostic biomarker in patients with frontotemporal dementia.Frontiers in aging neuroscience · 2023Article
- Reduced levels of NGF shift astrocytes toward a neurotoxic phenotype.Frontiers in cell and developmental biology · 2023Article
- The emerging role of furin in neurodegenerative and neuropsychiatric diseases.Translational neurodegeneration · 2022Review
- Review
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 1 country.
Funding
Abstract
ProNGF, the precursor of mature nerve growth factor (NGF), is the most abundant form of NGF in the brain. ProNGF and mature NGF differ significantly in their receptor interaction properties and in their bioactivity. ProNGF increases markedly in the cortex of Alzheimer's disease (AD) brains and proNGF\NGF imbalance has been postulated to play a role in neurodegeneration. However, a direct proof for a causal link between increased proNGF and AD neurodegeneration is lacking. In order to evaluate the consequences of increased levels of proNGF in the postnatal brain, transgenic mice expressing a furin cleavage-resistant form of proNGF, under the control of the neuron-specific mouse Thy1.2 promoter, were derived and characterized. Different transgenic lines displayed a phenotypic gradient of neurodegenerative severity features. We focused the analysis on the two lines TgproNGF#3 and TgproNGF#72, which shared learning and memory impairments in behavioral tests, cholinergic deficit and increased Aβ-peptide immunoreactivity. In addition, TgproNGF#3 mice developed Aβ oligomer immunoreactivity, as well as late diffuse astrocytosis. Both TgproNGF lines also display electrophysiological alterations related to spontaneous epileptic-like events. The results provide direct evidence that alterations in the proNGF/NGF balance in the adult brain can be an upstream driver of neurodegeneration, contributing to a circular loop linking alterations of proNGF/NGF equilibrium to excitatory/inhibitory synaptic imbalance and amyloid precursor protein (APP) dysmetabolism.
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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.