ArticleBrain : a journal of neurology2017
The chemokine CXCL12 mediates the anti-amyloidogenic action of painless human nerve growth factor.
Article in Brain : a journal of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
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- Toward an NGF-based therapy for Rett syndrome.Frontiers in neuroscience · 2026Review
- Sex-Dependent Long-Term Neurobehavioral Recovery in Experimental Neonatal Hypoxic-Ischemic Encephalopathy.Pharmacology research & perspectives · 2025Article
- Cholinotrophic basal forebrain connectome dysfunction in Down syndrome with and without dementia.iScience · 2025Article
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- Modulation of neuronal α1-adrenergic receptor reduces tauopathy and neuroinflammation by inhibiting the STING/NF-κB/NLRP3 signaling pathway in Alzheimer's disease mice.Journal of neuroinflammation · 2025Article
- CXCL12 Engages Cortical Inhibitory Neurons to Enhance Dendritic Spine Plasticity and Structured Network Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Nerve growth factor signaling tunes axon maintenance protein abundance and kinetics of Wallerian degeneration.Molecular biology of the cell · 2025Article
- Clinical-grade intranasal NGF fuels neurological and metabolic functions of Mecp2-deficient mice.Brain : a journal of neurology · 2025Article
- Delivery of Neuroregenerative Proteins to the Brain for Treatments of Neurodegenerative Brain Diseases.Life (Basel, Switzerland) · 2024Review
- Article
- Genetic Dissection of BDNF and TrkB Expression in Glial Cells.Biomolecules · 2024Article
- Reversal of neurological deficits by painless nerve growth factor in a mouse model of Rett syndrome.Brain : a journal of neurology · 2024Article
- Feasibility and therapeutical potential of local intracerebral encapsulated cell biodelivery of BDNF to AppAlzheimer's research & therapy · 2023Article
- Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer's Disease Mice.Journal of molecular neuroscience : MN · 2023Article
- Intranasal nerve growth factor for prevention and recovery of the outcomes of traumatic brain injury.Neural regeneration research · 2023Review
- Reduced levels of NGF shift astrocytes toward a neurotoxic phenotype.Frontiers in cell and developmental biology · 2023Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nerve growth factor is a therapeutic candidate for Alzheimer's disease. Due to its pain-inducing activity, in current clinical trials nerve growth factor is delivered locally into the brain by neurosurgery, but data on the efficacy of local nerve growth factor delivery in decreasing amyloid-β deposition are not available. To reduce the nerve growth factor pain-inducing side effects, thus avoiding the need for local brain injection, we developed human painless nerve growth factor (hNGFp), inspired by the human genetic disease hereditary sensory and autonomic neuropathy type V. hNGFp has identical neurotrophic potency as wild-type human nerve growth factor, but a 10-fold lower pain sensitizing activity. In this study we first mimicked, in the 5xFAD mouse model, the intraparenchymal delivery of hNGFp used in clinical trials and found it to be ineffective in decreasing amyloid-β plaque load. On the contrary, the same dose of hNGFp delivered intranasally, which was widely biodistributed in the brain and did not induce pain, showed a potent anti-amyloidogenic action and rescued synaptic plasticity and memory deficits. We found that hNGFp acts on glial cells, modulating inflammatory proteins such as the soluble TNFα receptor II and the chemokine CXCL12. We further established that the rescuing effect by hNGFp is mediated by CXCL12, as pharmacological inhibition of CXCL12 receptor CXCR4 occludes most of hNGFp effects. These findings have significant therapeutic implications: (i) we established that a widespread exposure of the brain is required for nerve growth factor to fully exert its neuroprotective actions; and (ii) we have identified a new anti-neurodegenerative pathway as a broad target for new therapeutic opportunities for neurodegenerative diseases.
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