ArticleMolecular psychiatry2021
The human brain NGF metabolic pathway is impaired in the pre-clinical and clinical continuum of Alzheimers disease.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 64 citations in OpenAlex.
- Personalized single-cell transcriptomics reveals molecular diversity in Alzheimer's disease.Nature communications · 2026Article
- BDNF-Hyaluronic Acid Hydrogel Promotes Neuronal Differentiation of Neural Stem Cells in Aβ-Induced Injury and 5×FAD Mice.Biomedicines · 2026Article
- Neurotrophins and Galectin-3: Hidden Keys in Neuroinflammation-A Narrative Review.International journal of molecular sciences · 2026Review
- 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
- Vitamin deficiencies and Alzheimer's disease: evidence and implications for supplementation.Frontiers in nutrition · 2026Review
- Application of Neurotrophic Factors as a Therapeutic Approach for Neurodegenerative Diseases.Experimental neurobiology · 2025Review
- Are pNF-H, IL-6, BDNF, and NSP Reliable Biomarkers of Cognitive Function in Prostate Cancer Patients?International journal of molecular sciences · 2025Article
- Targeting Neuroinflammation and Cognitive Decline: First-in-Class Dual Butyrylcholinesterase and p38α Mitogen-Activated Protein Kinase Inhibitors.Journal of medicinal chemistry · 2025Article
- Nerve growth factor: what can surgeons and oncologists learn from a neurological and psychological biomarker?Molecular medicine (Cambridge, Mass.) · 2025Review
- Oxytocin Intervention Mitigates Pathological and Behavioral Impairments in APP/PS1 Mice Subjected to Early Social Isolation.CNS neuroscience & therapeutics · 2025Article
- Nerve growth factor precursor alterations in neuron-derived extracellular vesicles from individuals with Down syndrome along the Alzheimer's disease continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Basal forebrain activation improves working memory in senescent monkeys.bioRxiv : the preprint server for biology · 2024Article
- New BDNF and NT-3 Cyclic Mimetics Concur with Copper to Activate Trophic Signaling Pathways as Potential Molecular Entities to Protect Old Brains from Neurodegeneration.Biomolecules · 2024Article
- Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.Signal transduction and targeted therapy · 2024Review
- The impact of astrocytic NF-κB on healthy and Alzheimer's disease brains.Scientific reports · 2024Article
- Role of nerve growth factor on cognitive impairment in patients with Alzheimer's disease carrying apolipoprotein E ε4.CNS neuroscience & therapeutics · 2024Article
- ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides.FEBS open bio · 2024Article
- Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice.Psychopharmacology · 2023Article
- Advances in Molecular Psychiatry - March 2023: mitochondrial function, stress, neuroinflammation - bipolar disorder, psychosis, and Alzheimer's disease.Molecular psychiatry · 2023Article
- Prefrontal parvalbumin interneurons deficits mediate early emotional dysfunction in Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
The NGF metabolic pathway entails the proteins that mature pro-nerve growth factor (proNGF) to NGF and those that degrade NGF. Basal forebrain cholinergic neurons require NGF for maintenance of cholinergic phenotype, are critical for cognition, and degenerate early in Alzheimer's disease (AD). In AD, NGF metabolism is altered, but it is not known whether this is an early phenomenon, nor how it relates to AD pathology and symptomology. We acquired dorsolateral/medial prefrontal cortex samples from individuals with Alzheimer's dementia, Mild Cognitive Impairment (MCI), or no cognitive impairment with high (HA-NCI) and low (LA-NCI) brain Aβ from the Religious Orders Study. Cortical proNGF protein, but not mRNA, was higher in AD, MCI, and HA-NCI, while mature NGF was lower. Plasminogen protein was higher in MCI and AD brain tissue, with plasminogen mRNA not likewise elevated, suggesting diminished activation of the proNGF convertase, plasmin. The plasminogen activator tPA was lower in HA-NCI while neuroserpin, the CNS tPA inhibitor, was higher in AD and MCI cortical samples. Matrix metalloproteinase 9 (MMP9), which degrades NGF, was overactive in MCI and AD. Transcription of the MMP9 inhibitor TIMP1 was lower in HA-NCI. ProNGF levels correlated with plasminogen, neuroserpin, and VAChT while NGF correlated with MMP9 activity. In NCI, proNGF correlated with cerebral Aβ and tau deposition and to cognitive performance. In summary, proNGF maturation is impaired in preclinical and clinical AD while mature NGF degradation is enhanced. These differences correlate with cognition, pathology, and cholinergic tone, and may suggest novel biomarkers and therapeutic targets.
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