ArticleProceedings of the National Academy of Sciences of the United States of America2001
Nontropic actions of neurotrophins: subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00017940 (A Phase I Study of Ex Vivo Nerve Growth Factor Gene Therapy for Alzheimer's Disease), which is not on this map. Cited by 36 papers.
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.
A Phase I Study of Ex Vivo Nerve Growth Factor Gene Therapy for Alzheimer's Disease
Who cites it
36 citing papers in PubMed, 114 citations in OpenAlex.
- Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease.JAMA neurology · 2015Trial
- From Lab Bench to Hope: Emerging Gene Therapies in Clinical Trials for Alzheimer's Disease.Molecular neurobiology · 2025Review
- Neurotrophin mimetics and tropomyosin kinase receptors: a futuristic pharmacological tool for Parkinson's.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Review
- Neurotrophic Factors as Regenerative Therapy for Neurodegenerative Diseases: Current Status, Challenges and Future Perspectives.International journal of molecular sciences · 2023Review
- Focused ultrasound delivery of a selective TrkA agonist rescues cholinergic function in a mouse model of Alzheimer's disease.Science advances · 2020Article
- Modulation of the p75 neurotrophin receptor suppresses age-related basal forebrain cholinergic neuron degeneration.Scientific reports · 2019Article
- Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits.Journal of neurophysiology · 2015Article
- Analgesic use in nonhuman primates undergoing neurosurgical procedures.Journal of the American Association for Laboratory Animal Science : JAALAS · 2013Review
- Increased encapsulated cell biodelivery of nerve growth factor in the brain by transposon-mediated gene transfer.Gene therapy · 2012Article
- Current advances in using neurotrophic factors to treat neurodegenerative disorders.Translational neurodegeneration · 2012Article
- Progress in the development of new drugs in Alzheimer's disease.The journal of nutrition, health & aging · 2011Article
- Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the Göttingen minipig basal forebrain.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Unique contributions of distinct cholinergic projections to motor cortical plasticity and learning.Cerebral cortex (New York, N.Y. : 1991) · 2010Article
- Alzheimer disease.Disease-a-month : DM · 2010Review
- Gene therapy in Alzheimer's disease - potential for disease modification.Journal of cellular and molecular medicine · 2010Review
- Viral vectors for neurotrophic factor delivery: a gene therapy approach for neurodegenerative diseases of the CNS.Pharmacological research · 2010Review
- The pro-apoptotic substance thapsigargin selectively stimulates re-growth of brain capillaries.Current neurovascular research · 2009Article
- The basal forebrain cholinergic system is required specifically for behaviorally mediated cortical map plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Effects of two years of conjugated equine estrogens on cholinergic neurons in young and middle-aged ovariectomized monkeys.Brain research · 2009Article
- Long-term reversal of cholinergic neuronal decline in aged non-human primates by lentiviral NGF gene delivery.Experimental neurology · 2009Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Normal aging is associated with a significant reduction in cognitive function across primate species. However, the structural and molecular basis for this age-related decline in neural function has yet to be defined clearly. Extensive cell loss does not occur as a consequence of normal aging in human and nonhuman primate species. More recent studies have demonstrated significant reductions in functional neuronal markers in subcortical brain regions in primates as a consequence of aging, including dopaminergic and cholinergic systems, although corresponding losses in cortical innervation from these neurons have not been investigated. In the present study, we report that aging is associated with a significant 25% reduction in cortical innervation by cholinergic systems in rhesus monkeys (P < 0.001). Further, these age-related reductions are ameliorated by cellular delivery of human nerve growth factor to cholinergic somata in the basal forebrain, restoring levels of cholinergic innervation in the cortex to those of young monkeys (P = 0.89). Thus, (i) aging is associated with a significant reduction in cortical cholinergic innervation; (ii) this reduction is reversible by growth-factor delivery; and (iii) growth factors can remodel axonal terminal fields at a distance, representing a nontropic action of growth factors in modulating adult neuronal structure and function (i.e., administration of growth factors to cholinergic somata significantly increases axon density in terminal fields). These findings are relevant to potential clinical uses of growth factors to treat neurological disorders.
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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.