ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Impact of the NGF maturation and degradation pathway on the cortical cholinergic system phenotype.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 101 citations in OpenAlex.
- Nerve growth factor responsive elements modulate immune cell inflammation and are dysregulated in an Alzheimer's disease mouse model.Frontiers in immunology · 2026Article
- NGF in Neuropathic Pain: Understanding Its Role and Therapeutic Opportunities.Current issues in molecular biology · 2025Review
- Unraveling the molecular basis of snake venom nerve growth factor: human TrkA recognition through molecular dynamics simulation and comparison with human nerve growth factor.Frontiers in bioinformatics · 2025Article
- Delivery of Neuroregenerative Proteins to the Brain for Treatments of Neurodegenerative Brain Diseases.Life (Basel, Switzerland) · 2024Review
- Dysregulation of neurotrophin expression in prefrontal cortex and nucleus basalis magnocellularis during and after adolescent intermittent ethanol exposure.Alcohol (Fayetteville, N.Y.) · 2024Article
- Role of nerve growth factor on cognitive impairment in patients with Alzheimer's disease carrying apolipoprotein E ε4.CNS neuroscience & therapeutics · 2024Article
- Modulation of the p75NTR during Adolescent Alcohol Exposure Prevents Cholinergic Neuronal Atrophy and Associated Acetylcholine Activity and Behavioral Dysfunction.International journal of molecular sciences · 2024Article
- Article
- The role of neurotrophic factors in novel, rapid psychiatric treatments.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Cholinergic Reinforcement Signaling Is Impaired by Amyloidosis Prior to Its Synaptic Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- New perspectives on the basal forebrain cholinergic system in Alzheimer's disease.Neuroscience and biobehavioral reviews · 2023Review
- Distinct conformational changes occur within the intrinsically unstructured pro-domain of pro-Nerve Growth Factor in the presence of ATP and MgProtein science : a publication of the Protein Society · 2023Article
- The Molecular Effects of Environmental Enrichment on Alzheimer's Disease.Molecular neurobiology · 2022Review
- The Role of Neurotrophin Signaling in Age-Related Cognitive Decline and Cognitive Diseases.International journal of molecular sciences · 2022Review
- Piperine Provides Neuroprotection against Kainic Acid-Induced Neurotoxicity via Maintaining NGF Signalling Pathway.Molecules (Basel, Switzerland) · 2022Article
- The Nerve Growth Factor Metabolic Pathway Dysregulation as Cause of Alzheimer's Cholinergic Atrophy.Cells · 2021Review
- The human brain NGF metabolic pathway is impaired in the pre-clinical and clinical continuum of Alzheimers disease.Molecular psychiatry · 2021Article
- Review
- Peptides Derived from Growth Factors to Treat Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Imbalance of nerve growth factor metabolism in aging women with overactive bladder syndrome.World journal of urology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Cortical cholinergic atrophy plays a significant role in the cognitive loss seen with aging and in Alzheimer's disease (AD), but the mechanisms leading to it remain unresolved. Nerve growth factor (NGF) is the neurotrophin responsible for the phenotypic maintenance of basal forebrain cholinergic neurons in the mature and fully differentiated CNS. In consequence, its implication in cholinergic atrophy has been suspected; however, no mechanistic explanation has been provided. We have previously shown that the precursor of NGF (proNGF) is cleaved extracellularly by plasmin to form mature NGF (mNGF) and that mNGF is degraded by matrix metalloproteinase 9. Using cognitive-behavioral tests, Western blotting, and confocal and electron microscopy, this study demonstrates that a pharmacologically induced chronic failure in extracellular NGF maturation leads to a reduction in mNGF levels, proNGF accumulation, cholinergic degeneration, and cognitive impairment in rats. It also shows that inhibiting NGF degradation increases endogenous levels of the mature neurotrophin and increases the density of cortical cholinergic boutons. Together, the data point to a mechanism explaining cholinergic loss in neurodegenerative conditions such as AD and provide a potential therapeutic target for the protection or restoration of this CNS transmitter system in aging and AD.
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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.